Multiple Sclerosis Hub

Symptoms of migraine aura may resemble those of multiple sclerosis (MS) relapse, and some MS drugs may cause headache.

STOWE, VT—Migraine and multiple sclerosis (MS) can have similar symptoms and often are comorbid diseases, according to Angela Applebee, MD, who spoke at the Headache Cooperative of New England’s 22nd Annual Headache Symposium. Neurologists should know which MS therapies can contribute to headache and which migraine drugs to prescribe with caution if a patient is taking certain new MS therapies, said Dr. Applebee, Assistant Professor of Neurology at the University of Vermont in Burlington.

The Link Between Migraine and MS
“The most convincing study of the link between migraine and MS” is the Nursing Health Study, said Dr. Applebee. That prospective study, during which investigators at New York University sent surveys to 116,000 nurses from 1989 to 1995, found that patients with migraine had a 39% higher risk of developing MS than nonmigraneurs. The absolute risk of developing MS was 0.15% higher, which means that migraine is a modest predictor of MS. Stronger predictors of MS include factors such as DRB1*1501 haplotype or history of infectious mononucleosis.

The study also found that patients with MS had a 33% greater chance of being diagnosed with migraine during follow-up. This difference was nonsignificant, however, said Dr. Applebee.

Differentiating Between Migraine Aura and MS Relapse
Migraine aura and MS relapse may have similar symptoms, but several principles can help neurologists distinguish between the two. First, aura tends not to last as long as MS relapse. In general, migraine aura lasts from five to 60 minutes, with the exception of the rare hemiplegic migraine variant. In MS relapse, on the other hand, new or worsening previous symptoms usually occur for 24 hours. “When I’m doing a history on a new patient, I’m trying to determine whether the symptom is always there, or whether it comes and goes, to help determine whether it could be a relapse or an aura,” Dr. Applebee explained.

Second, the symptoms of migraine aura tend to be consistent, but those of MS relapse tend to vary. A stress such as an infection, however, can cause an MS relapse characterized by a recurrence of old symptoms.

Also, each occurrence of migraine usually is related to the same areas of the brain. In contrast, each MS relapse, by definition, affects a different area of the brain than the previous MS relapse had affected. “If the optic nerve is first involved [in a relapse], another area of the brain should be next involved,” said Dr. Applebee. “Different areas of the brain don’t have to be involved in migraine,” she added.

Between 20% and 30% of auras entail visual and sensory disturbance. If an MS relapse entails a visual disturbance, it tends to include the symptoms of optic neuritis, such as pain when moving the eye and cloudy vision. MS relapses also may be associated with nystagmus or diplopia, said Dr. Applebee.

Drugs for MS May Cause Headache
Several drugs used to treat MS may cause headache. Natalizumab, a once-per-month infusion, can cause a postinfusion headache that lasts 24 hours before resolving itself completely. “If you premedicate prior to the infusion, this tends not to be an issue, and I haven’t seen that patients with migraine are more predisposed to having headaches with natalizumab,” advised Dr. Applebee.

Interferon therapies, which are given by subcutaneous or intramuscular injection, sometimes cause flulike symptoms that last from three to six months after the start of therapy. “If you teach patients to premedicate prior to their injections, it can minimize the flulike symptoms,” said Dr. Applebee. “Patients with migraine tend to have more difficulty in controlling their migraines when they first go on interferon therapy.” This difficulty, however, is not a contraindication for using interferon therapies in these patients, she added.

A patient with MS also may experience headache for the first four weeks after starting to take fingolimod, which the FDA approved in 2010. After four weeks, the headache usually resolves itself. Initiating treatment with fingolimod sometimes causes a pounding headache in patients with no previous history of headache. The drug also may make it difficult for patients with migraine to control their headache, but pulse steroids can provide relief, said Dr. Applebee.

Monitoring Fingolimod Use in Patients With Comorbid Cardiac Problems
Because fingolimod acts on the S1P1 receptors, patients may have a decreased heart rate within the first six hours of their first dose of the drug. The drug may lead to first- and second-degree heart block.

“When we dose these patients, we do a baseline ECG in our office, monitor them for six hours with vitals every hour, and then have a second ECG performed prior to exit,” noted Dr. Applebee. Patients with abnormal ECGs should be admitted to the hospital to ensure that they can tolerate the medication, she observed.

“In general, calcium-channel blockers and beta-blockers, if possible, should be avoided for migraine prophylactic therapy in these patients because of the possible interaction with fingolimod,” advised Dr. Applebee.

A recent study found that a beta-blocker in combination with fingolimod decreased heart rate to a statistically significant degree. A calcium-channel blocker did not have this effect, however, when it was administered with fingolimod. If a patient with MS and cardiac problems is taking fingolimod, a neurologist should consult his or her primary care doctor to determine the most appropriate medication for prophylaxis, concluded Dr. Applebee.   

Symptoms of migraine aura may resemble those of multiple sclerosis (MS) relapse, and some MS drugs may cause headache.

STOWE, VT—Migraine and multiple sclerosis (MS) can have similar symptoms and often are comorbid diseases, according to Angela Applebee, MD, who spoke at the Headache Cooperative of New England’s 22nd Annual Headache Symposium. Neurologists should know which MS therapies can contribute to headache and which migraine drugs to prescribe with caution if a patient is taking certain new MS therapies, said Dr. Applebee, Assistant Professor of Neurology at the University of Vermont in Burlington.

The Link Between Migraine and MS
“The most convincing study of the link between migraine and MS” is the Nursing Health Study, said Dr. Applebee. That prospective study, during which investigators at New York University sent surveys to 116,000 nurses from 1989 to 1995, found that patients with migraine had a 39% higher risk of developing MS than nonmigraneurs. The absolute risk of developing MS was 0.15% higher, which means that migraine is a modest predictor of MS. Stronger predictors of MS include factors such as DRB1*1501 haplotype or history of infectious mononucleosis.

The study also found that patients with MS had a 33% greater chance of being diagnosed with migraine during follow-up. This difference was nonsignificant, however, said Dr. Applebee.

Differentiating Between Migraine Aura and MS Relapse
Migraine aura and MS relapse may have similar symptoms, but several principles can help neurologists distinguish between the two. First, aura tends not to last as long as MS relapse. In general, migraine aura lasts from five to 60 minutes, with the exception of the rare hemiplegic migraine variant. In MS relapse, on the other hand, new or worsening previous symptoms usually occur for 24 hours. “When I’m doing a history on a new patient, I’m trying to determine whether the symptom is always there, or whether it comes and goes, to help determine whether it could be a relapse or an aura,” Dr. Applebee explained.

Second, the symptoms of migraine aura tend to be consistent, but those of MS relapse tend to vary. A stress such as an infection, however, can cause an MS relapse characterized by a recurrence of old symptoms.

Also, each occurrence of migraine usually is related to the same areas of the brain. In contrast, each MS relapse, by definition, affects a different area of the brain than the previous MS relapse had affected. “If the optic nerve is first involved [in a relapse], another area of the brain should be next involved,” said Dr. Applebee. “Different areas of the brain don’t have to be involved in migraine,” she added.

Between 20% and 30% of auras entail visual and sensory disturbance. If an MS relapse entails a visual disturbance, it tends to include the symptoms of optic neuritis, such as pain when moving the eye and cloudy vision. MS relapses also may be associated with nystagmus or diplopia, said Dr. Applebee.

Drugs for MS May Cause Headache
Several drugs used to treat MS may cause headache. Natalizumab, a once-per-month infusion, can cause a postinfusion headache that lasts 24 hours before resolving itself completely. “If you premedicate prior to the infusion, this tends not to be an issue, and I haven’t seen that patients with migraine are more predisposed to having headaches with natalizumab,” advised Dr. Applebee.

Interferon therapies, which are given by subcutaneous or intramuscular injection, sometimes cause flulike symptoms that last from three to six months after the start of therapy. “If you teach patients to premedicate prior to their injections, it can minimize the flulike symptoms,” said Dr. Applebee. “Patients with migraine tend to have more difficulty in controlling their migraines when they first go on interferon therapy.” This difficulty, however, is not a contraindication for using interferon therapies in these patients, she added.

A patient with MS also may experience headache for the first four weeks after starting to take fingolimod, which the FDA approved in 2010. After four weeks, the headache usually resolves itself. Initiating treatment with fingolimod sometimes causes a pounding headache in patients with no previous history of headache. The drug also may make it difficult for patients with migraine to control their headache, but pulse steroids can provide relief, said Dr. Applebee.

Monitoring Fingolimod Use in Patients With Comorbid Cardiac Problems
Because fingolimod acts on the S1P1 receptors, patients may have a decreased heart rate within the first six hours of their first dose of the drug. The drug may lead to first- and second-degree heart block.

“When we dose these patients, we do a baseline ECG in our office, monitor them for six hours with vitals every hour, and then have a second ECG performed prior to exit,” noted Dr. Applebee. Patients with abnormal ECGs should be admitted to the hospital to ensure that they can tolerate the medication, she observed.

“In general, calcium-channel blockers and beta-blockers, if possible, should be avoided for migraine prophylactic therapy in these patients because of the possible interaction with fingolimod,” advised Dr. Applebee.

A recent study found that a beta-blocker in combination with fingolimod decreased heart rate to a statistically significant degree. A calcium-channel blocker did not have this effect, however, when it was administered with fingolimod. If a patient with MS and cardiac problems is taking fingolimod, a neurologist should consult his or her primary care doctor to determine the most appropriate medication for prophylaxis, concluded Dr. Applebee.   

Symptoms of migraine aura may resemble those of multiple sclerosis (MS) relapse, and some MS drugs may cause headache.

STOWE, VT—Migraine and multiple sclerosis (MS) can have similar symptoms and often are comorbid diseases, according to Angela Applebee, MD, who spoke at the Headache Cooperative of New England’s 22nd Annual Headache Symposium. Neurologists should know which MS therapies can contribute to headache and which migraine drugs to prescribe with caution if a patient is taking certain new MS therapies, said Dr. Applebee, Assistant Professor of Neurology at the University of Vermont in Burlington.

The Link Between Migraine and MS
“The most convincing study of the link between migraine and MS” is the Nursing Health Study, said Dr. Applebee. That prospective study, during which investigators at New York University sent surveys to 116,000 nurses from 1989 to 1995, found that patients with migraine had a 39% higher risk of developing MS than nonmigraneurs. The absolute risk of developing MS was 0.15% higher, which means that migraine is a modest predictor of MS. Stronger predictors of MS include factors such as DRB1*1501 haplotype or history of infectious mononucleosis.

The study also found that patients with MS had a 33% greater chance of being diagnosed with migraine during follow-up. This difference was nonsignificant, however, said Dr. Applebee.

Differentiating Between Migraine Aura and MS Relapse
Migraine aura and MS relapse may have similar symptoms, but several principles can help neurologists distinguish between the two. First, aura tends not to last as long as MS relapse. In general, migraine aura lasts from five to 60 minutes, with the exception of the rare hemiplegic migraine variant. In MS relapse, on the other hand, new or worsening previous symptoms usually occur for 24 hours. “When I’m doing a history on a new patient, I’m trying to determine whether the symptom is always there, or whether it comes and goes, to help determine whether it could be a relapse or an aura,” Dr. Applebee explained.

Second, the symptoms of migraine aura tend to be consistent, but those of MS relapse tend to vary. A stress such as an infection, however, can cause an MS relapse characterized by a recurrence of old symptoms.

Also, each occurrence of migraine usually is related to the same areas of the brain. In contrast, each MS relapse, by definition, affects a different area of the brain than the previous MS relapse had affected. “If the optic nerve is first involved [in a relapse], another area of the brain should be next involved,” said Dr. Applebee. “Different areas of the brain don’t have to be involved in migraine,” she added.

Between 20% and 30% of auras entail visual and sensory disturbance. If an MS relapse entails a visual disturbance, it tends to include the symptoms of optic neuritis, such as pain when moving the eye and cloudy vision. MS relapses also may be associated with nystagmus or diplopia, said Dr. Applebee.

Drugs for MS May Cause Headache
Several drugs used to treat MS may cause headache. Natalizumab, a once-per-month infusion, can cause a postinfusion headache that lasts 24 hours before resolving itself completely. “If you premedicate prior to the infusion, this tends not to be an issue, and I haven’t seen that patients with migraine are more predisposed to having headaches with natalizumab,” advised Dr. Applebee.

Interferon therapies, which are given by subcutaneous or intramuscular injection, sometimes cause flulike symptoms that last from three to six months after the start of therapy. “If you teach patients to premedicate prior to their injections, it can minimize the flulike symptoms,” said Dr. Applebee. “Patients with migraine tend to have more difficulty in controlling their migraines when they first go on interferon therapy.” This difficulty, however, is not a contraindication for using interferon therapies in these patients, she added.

A patient with MS also may experience headache for the first four weeks after starting to take fingolimod, which the FDA approved in 2010. After four weeks, the headache usually resolves itself. Initiating treatment with fingolimod sometimes causes a pounding headache in patients with no previous history of headache. The drug also may make it difficult for patients with migraine to control their headache, but pulse steroids can provide relief, said Dr. Applebee.

Monitoring Fingolimod Use in Patients With Comorbid Cardiac Problems
Because fingolimod acts on the S1P1 receptors, patients may have a decreased heart rate within the first six hours of their first dose of the drug. The drug may lead to first- and second-degree heart block.

“When we dose these patients, we do a baseline ECG in our office, monitor them for six hours with vitals every hour, and then have a second ECG performed prior to exit,” noted Dr. Applebee. Patients with abnormal ECGs should be admitted to the hospital to ensure that they can tolerate the medication, she observed.

“In general, calcium-channel blockers and beta-blockers, if possible, should be avoided for migraine prophylactic therapy in these patients because of the possible interaction with fingolimod,” advised Dr. Applebee.

A recent study found that a beta-blocker in combination with fingolimod decreased heart rate to a statistically significant degree. A calcium-channel blocker did not have this effect, however, when it was administered with fingolimod. If a patient with MS and cardiac problems is taking fingolimod, a neurologist should consult his or her primary care doctor to determine the most appropriate medication for prophylaxis, concluded Dr. Applebee.   

Women ages 65 and older with retinopathy are more likely to have cognitive decline and larger ischemic lesion volumes, researchers reported in the March 14 online Neurology. Using fundus photography to assess retinopathy and the modified Mini-Mental State Examination (3MSE) to assess cognitive performance over time, the investigators studied 511 women who were enrolled in the Women’s Health Initiative Memory Study and the Sight Examination Study. After a 10-year follow-up period, women with retinopathy had lower 3MSE scores, 47% larger ischemic volumes in the total brain, and 68% larger ischemic volumes in the parietal lobe. According to the researchers, the association between retinopathy and cognitive impairment, as well as larger ischemic lesion volumes, “strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes.”
Regular use of statins is associated with a modest reduction in the risk of Parkinson’s disease, according to a study in the March Archives of Neurology. The prospective study included 38,192 men and 90,874 women participating in two ongoing US cohorts. Those enrolled were followed for 12 years, during which 644 cases (338 women) of Parkinson’s disease were documented. The investigators found that current statin users had a lower risk of Parkinson’s disease, compared with nonusers. Furthermore, participants younger than 60 at baseline had a significant association between Parkinson’s disease risk and statin use, while those who were older did not have such an association. “The possibility that some statins may reduce Parkinson’s disease risk deserves further consideration,” the study authors stated.

Labels for statin drugs will now include information about memory loss and confusion side effects experienced by some patients, according to changes issued by the FDA. The statin drugs include atorvastatin, fluvastatin, lovastatin, lovastatin extended-release, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as combination products. According to the FDA, the cognitive effects experienced by patients taking statins were usually not serious and were reversed by stopping statin use. In addition to describing cognitive effects, label changes to the statins will provide information on blood sugar increases experienced by some patients and regarding a greater risk of being diagnosed with type 2 diabetes mellitus. The updated labels also identify contraindications for lovastatin and remove the recommendation for routine periodic monitoring of liver enzymes in patients taking statins. The FDA emphasized that health care professionals and patients should be aware of the most current information on statin risks, while remaining assured that statins provide an important health benefit.

The FDA has approved the Avonex pen and a new dose titration regimen for once-a-week treatment of Avonex in patients with relapsing forms of multiple sclerosis (MS). Patients may experience less injection anxiety and pain by using the Avonex pen, which has an automated injection device and a smaller needle than the currently available Avonex Prefilled Syringe. Data from an open-label, multicenter, phase IIIb study showed that approximately nine of 10 patients successfully used the device, and 94% of patients preferred the Avonex pen to the Avonex Prefilled Syringe. In addition, a randomized, phase I study found that the new dose titration regimen, which gradually escalates the dose of Avonex (Biogen Idec; Weston, Massachusetts) at treatment initiation, reduced the incidence and severity of flulike symptoms.

Women who have multiple pregnancies may have a reduced risk of multiple sclerosis (MS), according to research published in the March 7 online Neurology. Investigators reviewed the cases of 282 men and women who had a first clinical diagnosis of CNS demyelination between 2003 and 2006. These 282 patients (ages 18 to 59) were compared with a matched control group of 542 patients who did not have a first clinical diagnosis of CNS demyelination. Among women, having a higher number of offspring was associated with a lower risk of a first clinical diagnosis of CNS demyelination. “These findings are consistent with a cumulative beneficial effect of pregnancy,” the study authors stated. They speculated that societal trends toward having children at a later age and having fewer children overall may help explain the increasing rate of MS cases in women.

Women ages 65 and older with retinopathy are more likely to have cognitive decline and larger ischemic lesion volumes, researchers reported in the March 14 online Neurology. Using fundus photography to assess retinopathy and the modified Mini-Mental State Examination (3MSE) to assess cognitive performance over time, the investigators studied 511 women who were enrolled in the Women’s Health Initiative Memory Study and the Sight Examination Study. After a 10-year follow-up period, women with retinopathy had lower 3MSE scores, 47% larger ischemic volumes in the total brain, and 68% larger ischemic volumes in the parietal lobe. According to the researchers, the association between retinopathy and cognitive impairment, as well as larger ischemic lesion volumes, “strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes.”
Regular use of statins is associated with a modest reduction in the risk of Parkinson’s disease, according to a study in the March Archives of Neurology. The prospective study included 38,192 men and 90,874 women participating in two ongoing US cohorts. Those enrolled were followed for 12 years, during which 644 cases (338 women) of Parkinson’s disease were documented. The investigators found that current statin users had a lower risk of Parkinson’s disease, compared with nonusers. Furthermore, participants younger than 60 at baseline had a significant association between Parkinson’s disease risk and statin use, while those who were older did not have such an association. “The possibility that some statins may reduce Parkinson’s disease risk deserves further consideration,” the study authors stated.

Labels for statin drugs will now include information about memory loss and confusion side effects experienced by some patients, according to changes issued by the FDA. The statin drugs include atorvastatin, fluvastatin, lovastatin, lovastatin extended-release, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as combination products. According to the FDA, the cognitive effects experienced by patients taking statins were usually not serious and were reversed by stopping statin use. In addition to describing cognitive effects, label changes to the statins will provide information on blood sugar increases experienced by some patients and regarding a greater risk of being diagnosed with type 2 diabetes mellitus. The updated labels also identify contraindications for lovastatin and remove the recommendation for routine periodic monitoring of liver enzymes in patients taking statins. The FDA emphasized that health care professionals and patients should be aware of the most current information on statin risks, while remaining assured that statins provide an important health benefit.

The FDA has approved the Avonex pen and a new dose titration regimen for once-a-week treatment of Avonex in patients with relapsing forms of multiple sclerosis (MS). Patients may experience less injection anxiety and pain by using the Avonex pen, which has an automated injection device and a smaller needle than the currently available Avonex Prefilled Syringe. Data from an open-label, multicenter, phase IIIb study showed that approximately nine of 10 patients successfully used the device, and 94% of patients preferred the Avonex pen to the Avonex Prefilled Syringe. In addition, a randomized, phase I study found that the new dose titration regimen, which gradually escalates the dose of Avonex (Biogen Idec; Weston, Massachusetts) at treatment initiation, reduced the incidence and severity of flulike symptoms.

Women who have multiple pregnancies may have a reduced risk of multiple sclerosis (MS), according to research published in the March 7 online Neurology. Investigators reviewed the cases of 282 men and women who had a first clinical diagnosis of CNS demyelination between 2003 and 2006. These 282 patients (ages 18 to 59) were compared with a matched control group of 542 patients who did not have a first clinical diagnosis of CNS demyelination. Among women, having a higher number of offspring was associated with a lower risk of a first clinical diagnosis of CNS demyelination. “These findings are consistent with a cumulative beneficial effect of pregnancy,” the study authors stated. They speculated that societal trends toward having children at a later age and having fewer children overall may help explain the increasing rate of MS cases in women.

Women ages 65 and older with retinopathy are more likely to have cognitive decline and larger ischemic lesion volumes, researchers reported in the March 14 online Neurology. Using fundus photography to assess retinopathy and the modified Mini-Mental State Examination (3MSE) to assess cognitive performance over time, the investigators studied 511 women who were enrolled in the Women’s Health Initiative Memory Study and the Sight Examination Study. After a 10-year follow-up period, women with retinopathy had lower 3MSE scores, 47% larger ischemic volumes in the total brain, and 68% larger ischemic volumes in the parietal lobe. According to the researchers, the association between retinopathy and cognitive impairment, as well as larger ischemic lesion volumes, “strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes.”
Regular use of statins is associated with a modest reduction in the risk of Parkinson’s disease, according to a study in the March Archives of Neurology. The prospective study included 38,192 men and 90,874 women participating in two ongoing US cohorts. Those enrolled were followed for 12 years, during which 644 cases (338 women) of Parkinson’s disease were documented. The investigators found that current statin users had a lower risk of Parkinson’s disease, compared with nonusers. Furthermore, participants younger than 60 at baseline had a significant association between Parkinson’s disease risk and statin use, while those who were older did not have such an association. “The possibility that some statins may reduce Parkinson’s disease risk deserves further consideration,” the study authors stated.

Labels for statin drugs will now include information about memory loss and confusion side effects experienced by some patients, according to changes issued by the FDA. The statin drugs include atorvastatin, fluvastatin, lovastatin, lovastatin extended-release, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as combination products. According to the FDA, the cognitive effects experienced by patients taking statins were usually not serious and were reversed by stopping statin use. In addition to describing cognitive effects, label changes to the statins will provide information on blood sugar increases experienced by some patients and regarding a greater risk of being diagnosed with type 2 diabetes mellitus. The updated labels also identify contraindications for lovastatin and remove the recommendation for routine periodic monitoring of liver enzymes in patients taking statins. The FDA emphasized that health care professionals and patients should be aware of the most current information on statin risks, while remaining assured that statins provide an important health benefit.

The FDA has approved the Avonex pen and a new dose titration regimen for once-a-week treatment of Avonex in patients with relapsing forms of multiple sclerosis (MS). Patients may experience less injection anxiety and pain by using the Avonex pen, which has an automated injection device and a smaller needle than the currently available Avonex Prefilled Syringe. Data from an open-label, multicenter, phase IIIb study showed that approximately nine of 10 patients successfully used the device, and 94% of patients preferred the Avonex pen to the Avonex Prefilled Syringe. In addition, a randomized, phase I study found that the new dose titration regimen, which gradually escalates the dose of Avonex (Biogen Idec; Weston, Massachusetts) at treatment initiation, reduced the incidence and severity of flulike symptoms.

Women who have multiple pregnancies may have a reduced risk of multiple sclerosis (MS), according to research published in the March 7 online Neurology. Investigators reviewed the cases of 282 men and women who had a first clinical diagnosis of CNS demyelination between 2003 and 2006. These 282 patients (ages 18 to 59) were compared with a matched control group of 542 patients who did not have a first clinical diagnosis of CNS demyelination. Among women, having a higher number of offspring was associated with a lower risk of a first clinical diagnosis of CNS demyelination. “These findings are consistent with a cumulative beneficial effect of pregnancy,” the study authors stated. They speculated that societal trends toward having children at a later age and having fewer children overall may help explain the increasing rate of MS cases in women.

Although measles antibody levels decrease in the general population, an increase is evident in the serum and CSF of patients with MS.

AMSTERDAM—The level of measles virus antibody increases with age and duration of multiple sclerosis (MS) in the serum and CSF of patients with MS, according to research presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).

The synthesis of measles antibodies continues to increase many years after MS has been diagnosed, according to the study. In healthy controls, however, levels of measles antibody decrease slightly with age.

Comparing Antibody Titres in MS Patients and the General Population
After a healthy person is infected with or vaccinated against measles, his or her measles antibody titres decrease over time. But most patients with MS have higher measles antibody titres in their serum and CSF than the general population does, according to Cecilia Ahlgren, PhD, of the Institute of Clinical Neuroscience at Sahlgrenska University Hospital in Gothenburg, Sweden.

Dr. Ahlgren and her colleagues tested the level of measles antibody in the serum and CSF of 161 patients with MS between the ages of 15 and 49. The age of MS onset among the patients ranged from 10 to 39.

The team included a control group of 50 healthy blood donors who each gave samples of their serum and CSF. Members of the control group ranged in age from 18 to 57.

The investigators sought to determine whether increased synthesis of measles antibody was a systemic phenomenon or was confined to the CSF. They analyzed the levels of measles antibody in serum and CSF through enzyme-linked immunosorbent assay. The researchers then analyzed correlations between antibody titres and age, and antibody titres and MS duration using linear regression.

MS May Sound a General Alarm in the Body
Measles antibody levels increased with age and MS duration, and antibody synthesis occurred in the CSF and serum, according to Dr. Ahlgren and her colleagues. Increasing measles antibody titres are most likely “part of a polyspecific immune response, probably with no pathogenic role,” they wrote.

B cells and plasma cells are considered important in the production of antibodies, but the researchers were not certain about whether B cell follicles caused the increased antibody production seen in the study. Because increased antibody titres were found in the serum as well as the CSF, “our results point to a more general activation of B cells and plasma cells,” concluded the investigators.

Although measles antibody levels decrease in the general population, an increase is evident in the serum and CSF of patients with MS.

AMSTERDAM—The level of measles virus antibody increases with age and duration of multiple sclerosis (MS) in the serum and CSF of patients with MS, according to research presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).

The synthesis of measles antibodies continues to increase many years after MS has been diagnosed, according to the study. In healthy controls, however, levels of measles antibody decrease slightly with age.

Comparing Antibody Titres in MS Patients and the General Population
After a healthy person is infected with or vaccinated against measles, his or her measles antibody titres decrease over time. But most patients with MS have higher measles antibody titres in their serum and CSF than the general population does, according to Cecilia Ahlgren, PhD, of the Institute of Clinical Neuroscience at Sahlgrenska University Hospital in Gothenburg, Sweden.

Dr. Ahlgren and her colleagues tested the level of measles antibody in the serum and CSF of 161 patients with MS between the ages of 15 and 49. The age of MS onset among the patients ranged from 10 to 39.

The team included a control group of 50 healthy blood donors who each gave samples of their serum and CSF. Members of the control group ranged in age from 18 to 57.

The investigators sought to determine whether increased synthesis of measles antibody was a systemic phenomenon or was confined to the CSF. They analyzed the levels of measles antibody in serum and CSF through enzyme-linked immunosorbent assay. The researchers then analyzed correlations between antibody titres and age, and antibody titres and MS duration using linear regression.

MS May Sound a General Alarm in the Body
Measles antibody levels increased with age and MS duration, and antibody synthesis occurred in the CSF and serum, according to Dr. Ahlgren and her colleagues. Increasing measles antibody titres are most likely “part of a polyspecific immune response, probably with no pathogenic role,” they wrote.

B cells and plasma cells are considered important in the production of antibodies, but the researchers were not certain about whether B cell follicles caused the increased antibody production seen in the study. Because increased antibody titres were found in the serum as well as the CSF, “our results point to a more general activation of B cells and plasma cells,” concluded the investigators.

Although measles antibody levels decrease in the general population, an increase is evident in the serum and CSF of patients with MS.

AMSTERDAM—The level of measles virus antibody increases with age and duration of multiple sclerosis (MS) in the serum and CSF of patients with MS, according to research presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).

The synthesis of measles antibodies continues to increase many years after MS has been diagnosed, according to the study. In healthy controls, however, levels of measles antibody decrease slightly with age.

Comparing Antibody Titres in MS Patients and the General Population
After a healthy person is infected with or vaccinated against measles, his or her measles antibody titres decrease over time. But most patients with MS have higher measles antibody titres in their serum and CSF than the general population does, according to Cecilia Ahlgren, PhD, of the Institute of Clinical Neuroscience at Sahlgrenska University Hospital in Gothenburg, Sweden.

Dr. Ahlgren and her colleagues tested the level of measles antibody in the serum and CSF of 161 patients with MS between the ages of 15 and 49. The age of MS onset among the patients ranged from 10 to 39.

The team included a control group of 50 healthy blood donors who each gave samples of their serum and CSF. Members of the control group ranged in age from 18 to 57.

The investigators sought to determine whether increased synthesis of measles antibody was a systemic phenomenon or was confined to the CSF. They analyzed the levels of measles antibody in serum and CSF through enzyme-linked immunosorbent assay. The researchers then analyzed correlations between antibody titres and age, and antibody titres and MS duration using linear regression.

MS May Sound a General Alarm in the Body
Measles antibody levels increased with age and MS duration, and antibody synthesis occurred in the CSF and serum, according to Dr. Ahlgren and her colleagues. Increasing measles antibody titres are most likely “part of a polyspecific immune response, probably with no pathogenic role,” they wrote.

B cells and plasma cells are considered important in the production of antibodies, but the researchers were not certain about whether B cell follicles caused the increased antibody production seen in the study. Because increased antibody titres were found in the serum as well as the CSF, “our results point to a more general activation of B cells and plasma cells,” concluded the investigators.

Studies show that gray matter atrophy correlates with disability progression and drives whole brain atrophy in MS.

AMSTERDAM—Gray matter atrophy may serve as an effective outcome measure for clinical trials in multiple sclerosis (MS), said Richard A. Rudick, MD, Vice Chair of the Neurological Institute at the Cleveland Clinic. He described the latest research on gray matter atrophy at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).
According to Dr. Rudick, conventional MRI techniques almost entirely overlook gray matter pathology, even though 65% of the brain is composed of gray matter. “As a result, all of our focus has been on white matter, and the conventional MRI really just visualizes a small portion of the underlying pathology. [Gray matter pathology] is truly a Trojan horse in MS.”

Although gray matter lesions are still difficult to measure and not discernable using traditional MRI, gray matter atrophy appears to be a highly feasible metric for indirectly determining the impact of gray matter lesions. “Gray matter atrophy can be measured precisely with available techniques,” said Dr. Rudick.

Dr. Rudick described the clinical relevance of gray matter atrophy in MS, including how it correlates with lesions, disability, and whole brain atrophy, as well as its potential to mitigate complications when used as an outcome metric for MS clinical trials.

Resolving Pseudoatrophy Complications
Previous studies have attempted to use whole brain atrophy as a clinical trial measure, but these efforts have been complicated by the issue of pseudoatrophy, which occurs when MS therapies resolve edema and cause a rapid loss of tissue that resembles atrophy.

However, a recent posthoc analysis showed that pseudoatrophy was found in white matter rather than in gray matter. “So the significance of this, I believe, is that there doesn’t appear to be as much fluid shift in the gray matter as in the white matter,” Dr. Rudick commented. “And I think this [difference] would significantly simplify the design of clinical trials focused on atrophy if we were to focus on gray matter.”

Based on initial sample calculations, Dr. Rudick expects that future studies will require 60 to 80 patients per arm for moderate effect sizes.

Gray Matter Atrophy Influences Whole Brain Atrophy
Gray matter atrophy may serve as a valuable clinical trial metric, because it occurs early in the course of MS and increases as the disease advances, Dr. Rudick explained.

Data from an ongoing longitudinal study by Elizabeth Fisher, PhD, of the Cleveland Clinic Lerner Research Institute, and colleagues, suggest that accelerating whole brain atrophy over time is mostly driven by gray matter atrophy. The study is comparing healthy controls with patients progressing from clinically isolated syndrome to relapsing-remitting MS, as well as secondary and secondary progressive MS.

Dr. Rudick noted that white matter atrophy showed little change during the four-year study period. However, “when we look at the gray matter atrophy, it explodes, actually. It goes up to fourteenfold, compared with the healthy controls. So the accelerating atrophy over time is largely driven by increasing gray matter atrophy.”

Correlation With Disability
Gray matter atrophy also correlates with MS disability progression, according to six recent cross-sectional studies. In some of the studies, researchers analyzed multiple regression models and found that gray matter fraction, a method of quantifying gray matter atrophy, correlated with clinical outcomes better than other MRI variables, including white matter atrophy.

In addition, seven longitudinal studies have consistently demonstrated that gray matter atrophy shows a stronger correlation with disability progression than does white matter atrophy or lesions. Of the studies, two found that gray matter atrophy predicted conversion from clinically isolated syndrome to MS.

Modest Correlation With Lesions
Researchers have found that gray matter atrophy correlates somewhat with lesions as well. A three-year longitudinal study by Calabrese observed 76 patients with relapsing-remitting MS and 31 patients with secondary progressive MS. The investigators determined that cortical lesions at baseline predicted a change in gray matter volume, though the effect was modest in patients with relapsing-remitting MS and was not significant in patients with secondary progressive MS.

“My interpretation of this is that there is a connection between cortical lesions and cortical atrophy, but, at least using current techniques, this relationship is rather weak,” said Dr. Rudick. He pointed out that current methods for quantifying gray matter volume, such as gray matter fractional volume, may sometimes misclassify lesions due to their signal intensity. The potential for misclassification becomes more problematic in cases of advancing MS with numerous lesions.

In relation to quantifying gray matter atrophy, “it’s not clear whether gray matter fraction or cortical thickness or region of interest is the optimal approach,” said Dr. Rudick.

He also noted that the effect of drugs on gray matter atrophy might be of interest to researchers. However, not enough data are available to draw conclusions.

Looking forward, he suggested that gray matter atrophy may play an important role in future clinical trials. “I believe gray matter atrophy is an attractive outcome measure for MS clinical trials, because it seems to be very important, it’s feasible, and I think it should be fairly straightforward,” concluded Dr. Rudick.   

Studies show that gray matter atrophy correlates with disability progression and drives whole brain atrophy in MS.

AMSTERDAM—Gray matter atrophy may serve as an effective outcome measure for clinical trials in multiple sclerosis (MS), said Richard A. Rudick, MD, Vice Chair of the Neurological Institute at the Cleveland Clinic. He described the latest research on gray matter atrophy at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).
According to Dr. Rudick, conventional MRI techniques almost entirely overlook gray matter pathology, even though 65% of the brain is composed of gray matter. “As a result, all of our focus has been on white matter, and the conventional MRI really just visualizes a small portion of the underlying pathology. [Gray matter pathology] is truly a Trojan horse in MS.”

Although gray matter lesions are still difficult to measure and not discernable using traditional MRI, gray matter atrophy appears to be a highly feasible metric for indirectly determining the impact of gray matter lesions. “Gray matter atrophy can be measured precisely with available techniques,” said Dr. Rudick.

Dr. Rudick described the clinical relevance of gray matter atrophy in MS, including how it correlates with lesions, disability, and whole brain atrophy, as well as its potential to mitigate complications when used as an outcome metric for MS clinical trials.

Resolving Pseudoatrophy Complications
Previous studies have attempted to use whole brain atrophy as a clinical trial measure, but these efforts have been complicated by the issue of pseudoatrophy, which occurs when MS therapies resolve edema and cause a rapid loss of tissue that resembles atrophy.

However, a recent posthoc analysis showed that pseudoatrophy was found in white matter rather than in gray matter. “So the significance of this, I believe, is that there doesn’t appear to be as much fluid shift in the gray matter as in the white matter,” Dr. Rudick commented. “And I think this [difference] would significantly simplify the design of clinical trials focused on atrophy if we were to focus on gray matter.”

Based on initial sample calculations, Dr. Rudick expects that future studies will require 60 to 80 patients per arm for moderate effect sizes.

Gray Matter Atrophy Influences Whole Brain Atrophy
Gray matter atrophy may serve as a valuable clinical trial metric, because it occurs early in the course of MS and increases as the disease advances, Dr. Rudick explained.

Data from an ongoing longitudinal study by Elizabeth Fisher, PhD, of the Cleveland Clinic Lerner Research Institute, and colleagues, suggest that accelerating whole brain atrophy over time is mostly driven by gray matter atrophy. The study is comparing healthy controls with patients progressing from clinically isolated syndrome to relapsing-remitting MS, as well as secondary and secondary progressive MS.

Dr. Rudick noted that white matter atrophy showed little change during the four-year study period. However, “when we look at the gray matter atrophy, it explodes, actually. It goes up to fourteenfold, compared with the healthy controls. So the accelerating atrophy over time is largely driven by increasing gray matter atrophy.”

Correlation With Disability
Gray matter atrophy also correlates with MS disability progression, according to six recent cross-sectional studies. In some of the studies, researchers analyzed multiple regression models and found that gray matter fraction, a method of quantifying gray matter atrophy, correlated with clinical outcomes better than other MRI variables, including white matter atrophy.

In addition, seven longitudinal studies have consistently demonstrated that gray matter atrophy shows a stronger correlation with disability progression than does white matter atrophy or lesions. Of the studies, two found that gray matter atrophy predicted conversion from clinically isolated syndrome to MS.

Modest Correlation With Lesions
Researchers have found that gray matter atrophy correlates somewhat with lesions as well. A three-year longitudinal study by Calabrese observed 76 patients with relapsing-remitting MS and 31 patients with secondary progressive MS. The investigators determined that cortical lesions at baseline predicted a change in gray matter volume, though the effect was modest in patients with relapsing-remitting MS and was not significant in patients with secondary progressive MS.

“My interpretation of this is that there is a connection between cortical lesions and cortical atrophy, but, at least using current techniques, this relationship is rather weak,” said Dr. Rudick. He pointed out that current methods for quantifying gray matter volume, such as gray matter fractional volume, may sometimes misclassify lesions due to their signal intensity. The potential for misclassification becomes more problematic in cases of advancing MS with numerous lesions.

In relation to quantifying gray matter atrophy, “it’s not clear whether gray matter fraction or cortical thickness or region of interest is the optimal approach,” said Dr. Rudick.

He also noted that the effect of drugs on gray matter atrophy might be of interest to researchers. However, not enough data are available to draw conclusions.

Looking forward, he suggested that gray matter atrophy may play an important role in future clinical trials. “I believe gray matter atrophy is an attractive outcome measure for MS clinical trials, because it seems to be very important, it’s feasible, and I think it should be fairly straightforward,” concluded Dr. Rudick.   

Studies show that gray matter atrophy correlates with disability progression and drives whole brain atrophy in MS.

AMSTERDAM—Gray matter atrophy may serve as an effective outcome measure for clinical trials in multiple sclerosis (MS), said Richard A. Rudick, MD, Vice Chair of the Neurological Institute at the Cleveland Clinic. He described the latest research on gray matter atrophy at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).
According to Dr. Rudick, conventional MRI techniques almost entirely overlook gray matter pathology, even though 65% of the brain is composed of gray matter. “As a result, all of our focus has been on white matter, and the conventional MRI really just visualizes a small portion of the underlying pathology. [Gray matter pathology] is truly a Trojan horse in MS.”

Although gray matter lesions are still difficult to measure and not discernable using traditional MRI, gray matter atrophy appears to be a highly feasible metric for indirectly determining the impact of gray matter lesions. “Gray matter atrophy can be measured precisely with available techniques,” said Dr. Rudick.

Dr. Rudick described the clinical relevance of gray matter atrophy in MS, including how it correlates with lesions, disability, and whole brain atrophy, as well as its potential to mitigate complications when used as an outcome metric for MS clinical trials.

Resolving Pseudoatrophy Complications
Previous studies have attempted to use whole brain atrophy as a clinical trial measure, but these efforts have been complicated by the issue of pseudoatrophy, which occurs when MS therapies resolve edema and cause a rapid loss of tissue that resembles atrophy.

However, a recent posthoc analysis showed that pseudoatrophy was found in white matter rather than in gray matter. “So the significance of this, I believe, is that there doesn’t appear to be as much fluid shift in the gray matter as in the white matter,” Dr. Rudick commented. “And I think this [difference] would significantly simplify the design of clinical trials focused on atrophy if we were to focus on gray matter.”

Based on initial sample calculations, Dr. Rudick expects that future studies will require 60 to 80 patients per arm for moderate effect sizes.

Gray Matter Atrophy Influences Whole Brain Atrophy
Gray matter atrophy may serve as a valuable clinical trial metric, because it occurs early in the course of MS and increases as the disease advances, Dr. Rudick explained.

Data from an ongoing longitudinal study by Elizabeth Fisher, PhD, of the Cleveland Clinic Lerner Research Institute, and colleagues, suggest that accelerating whole brain atrophy over time is mostly driven by gray matter atrophy. The study is comparing healthy controls with patients progressing from clinically isolated syndrome to relapsing-remitting MS, as well as secondary and secondary progressive MS.

Dr. Rudick noted that white matter atrophy showed little change during the four-year study period. However, “when we look at the gray matter atrophy, it explodes, actually. It goes up to fourteenfold, compared with the healthy controls. So the accelerating atrophy over time is largely driven by increasing gray matter atrophy.”

Correlation With Disability
Gray matter atrophy also correlates with MS disability progression, according to six recent cross-sectional studies. In some of the studies, researchers analyzed multiple regression models and found that gray matter fraction, a method of quantifying gray matter atrophy, correlated with clinical outcomes better than other MRI variables, including white matter atrophy.

In addition, seven longitudinal studies have consistently demonstrated that gray matter atrophy shows a stronger correlation with disability progression than does white matter atrophy or lesions. Of the studies, two found that gray matter atrophy predicted conversion from clinically isolated syndrome to MS.

Modest Correlation With Lesions
Researchers have found that gray matter atrophy correlates somewhat with lesions as well. A three-year longitudinal study by Calabrese observed 76 patients with relapsing-remitting MS and 31 patients with secondary progressive MS. The investigators determined that cortical lesions at baseline predicted a change in gray matter volume, though the effect was modest in patients with relapsing-remitting MS and was not significant in patients with secondary progressive MS.

“My interpretation of this is that there is a connection between cortical lesions and cortical atrophy, but, at least using current techniques, this relationship is rather weak,” said Dr. Rudick. He pointed out that current methods for quantifying gray matter volume, such as gray matter fractional volume, may sometimes misclassify lesions due to their signal intensity. The potential for misclassification becomes more problematic in cases of advancing MS with numerous lesions.

In relation to quantifying gray matter atrophy, “it’s not clear whether gray matter fraction or cortical thickness or region of interest is the optimal approach,” said Dr. Rudick.

He also noted that the effect of drugs on gray matter atrophy might be of interest to researchers. However, not enough data are available to draw conclusions.

Looking forward, he suggested that gray matter atrophy may play an important role in future clinical trials. “I believe gray matter atrophy is an attractive outcome measure for MS clinical trials, because it seems to be very important, it’s feasible, and I think it should be fairly straightforward,” concluded Dr. Rudick.   

A referral to a neurologist may be a mitigating factor for expanded treatment with medication among patients with MS.

AMSTERDAM—About half of insured patients with multiple sclerosis (MS) in the United States do not take disease-modifying drugs within four years of diagnosis, according to a study presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Comorbid conditions, such as depression and inflammatory arthritis, may influence patients’ decision not to use medication. Consultation with a neurologist, however, was associated with expanded use of therapeutic drugs, which increased yearly, according to the study.

The reasons that so many patients with MS do not take medication are unclear. “Some of these patients had not seen a neurologist. Some had forms of MS where there is no treatment. Others have mild MS and preferred no treatment,” Lawrence Steinman, MD, Professor of Neurology and Neurological Sciences at the Stanford University School of Medicine in Palo Alto, California, told Neurology Reviews. “These are just speculative comments,” he added.

Although the benefits of pharmaceutical treatments for MS have been established, it is uncertain which patient populations are more likely to take disease-modifying drugs. A group led by Dr. Steinman studied insurance claims to determine the patient characteristics associated with use of therapeutic drugs.

Using insurance claims made between January 1, 2005, and December 31, 2007, the researchers created a cohort of 32,083 patients with MS, each of whom had had six months of continuous insurance coverage before filling his or her first prescription. The patients’ mean age was roughly 45, and about 75% of patients were female. The team excluded from the study patients first dispensed with immunosuppressants or other medicines.

Among patients treated with a drug, 9,541 first used interferon agents, and 5,212 began by using glatiramer acetate. During the six-month baseline period, the mean age of the treated patients was 45. The cohort included 16,434 patients who used no therapy during the observation period. The mean age of untreated patients during the six-month baseline period was 46.

A greater proportion (ie, 56%) of treated patients than nontreated patients (ie, 37%) was employed full time. Between 0.8% and 1.3% of treated patients filed a long-term disability claim, compared with 0.6% of the nontreated group. About 55% of treated patients visited a neurologist, compared with 46% of nontreated patients.

Dr. Steinman and his colleagues predicted patients’ use of interferon agents or glatiramer acetate in a logistic regression using patients’ baseline variables (eg, age, gender, comorbidities, and geographic region).

A greater proportion of patients in the northeast (ie, 53%) used disease-modifying drugs than in any other region of the US. The south had the lowest percentage of treated patients (ie, 45%). Patients who previously had used interferon or glatiramer acetate were much more likely to use a drug than patients who had not, according to the study.

A referral to a neurologist may be a mitigating factor for expanded treatment with medication among patients with MS.

AMSTERDAM—About half of insured patients with multiple sclerosis (MS) in the United States do not take disease-modifying drugs within four years of diagnosis, according to a study presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Comorbid conditions, such as depression and inflammatory arthritis, may influence patients’ decision not to use medication. Consultation with a neurologist, however, was associated with expanded use of therapeutic drugs, which increased yearly, according to the study.

The reasons that so many patients with MS do not take medication are unclear. “Some of these patients had not seen a neurologist. Some had forms of MS where there is no treatment. Others have mild MS and preferred no treatment,” Lawrence Steinman, MD, Professor of Neurology and Neurological Sciences at the Stanford University School of Medicine in Palo Alto, California, told Neurology Reviews. “These are just speculative comments,” he added.

Although the benefits of pharmaceutical treatments for MS have been established, it is uncertain which patient populations are more likely to take disease-modifying drugs. A group led by Dr. Steinman studied insurance claims to determine the patient characteristics associated with use of therapeutic drugs.

Using insurance claims made between January 1, 2005, and December 31, 2007, the researchers created a cohort of 32,083 patients with MS, each of whom had had six months of continuous insurance coverage before filling his or her first prescription. The patients’ mean age was roughly 45, and about 75% of patients were female. The team excluded from the study patients first dispensed with immunosuppressants or other medicines.

Among patients treated with a drug, 9,541 first used interferon agents, and 5,212 began by using glatiramer acetate. During the six-month baseline period, the mean age of the treated patients was 45. The cohort included 16,434 patients who used no therapy during the observation period. The mean age of untreated patients during the six-month baseline period was 46.

A greater proportion (ie, 56%) of treated patients than nontreated patients (ie, 37%) was employed full time. Between 0.8% and 1.3% of treated patients filed a long-term disability claim, compared with 0.6% of the nontreated group. About 55% of treated patients visited a neurologist, compared with 46% of nontreated patients.

Dr. Steinman and his colleagues predicted patients’ use of interferon agents or glatiramer acetate in a logistic regression using patients’ baseline variables (eg, age, gender, comorbidities, and geographic region).

A greater proportion of patients in the northeast (ie, 53%) used disease-modifying drugs than in any other region of the US. The south had the lowest percentage of treated patients (ie, 45%). Patients who previously had used interferon or glatiramer acetate were much more likely to use a drug than patients who had not, according to the study.

A referral to a neurologist may be a mitigating factor for expanded treatment with medication among patients with MS.

AMSTERDAM—About half of insured patients with multiple sclerosis (MS) in the United States do not take disease-modifying drugs within four years of diagnosis, according to a study presented at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Comorbid conditions, such as depression and inflammatory arthritis, may influence patients’ decision not to use medication. Consultation with a neurologist, however, was associated with expanded use of therapeutic drugs, which increased yearly, according to the study.

The reasons that so many patients with MS do not take medication are unclear. “Some of these patients had not seen a neurologist. Some had forms of MS where there is no treatment. Others have mild MS and preferred no treatment,” Lawrence Steinman, MD, Professor of Neurology and Neurological Sciences at the Stanford University School of Medicine in Palo Alto, California, told Neurology Reviews. “These are just speculative comments,” he added.

Although the benefits of pharmaceutical treatments for MS have been established, it is uncertain which patient populations are more likely to take disease-modifying drugs. A group led by Dr. Steinman studied insurance claims to determine the patient characteristics associated with use of therapeutic drugs.

Using insurance claims made between January 1, 2005, and December 31, 2007, the researchers created a cohort of 32,083 patients with MS, each of whom had had six months of continuous insurance coverage before filling his or her first prescription. The patients’ mean age was roughly 45, and about 75% of patients were female. The team excluded from the study patients first dispensed with immunosuppressants or other medicines.

Among patients treated with a drug, 9,541 first used interferon agents, and 5,212 began by using glatiramer acetate. During the six-month baseline period, the mean age of the treated patients was 45. The cohort included 16,434 patients who used no therapy during the observation period. The mean age of untreated patients during the six-month baseline period was 46.

A greater proportion (ie, 56%) of treated patients than nontreated patients (ie, 37%) was employed full time. Between 0.8% and 1.3% of treated patients filed a long-term disability claim, compared with 0.6% of the nontreated group. About 55% of treated patients visited a neurologist, compared with 46% of nontreated patients.

Dr. Steinman and his colleagues predicted patients’ use of interferon agents or glatiramer acetate in a logistic regression using patients’ baseline variables (eg, age, gender, comorbidities, and geographic region).

A greater proportion of patients in the northeast (ie, 53%) used disease-modifying drugs than in any other region of the US. The south had the lowest percentage of treated patients (ie, 45%). Patients who previously had used interferon or glatiramer acetate were much more likely to use a drug than patients who had not, according to the study.

Patients with early-stage multiple sclerosis (MS) show cortical demyelinating lesions that are numerous, inflammatory, and strongly linked with meningeal inflammation, according to a study published in the December 8, 2011, New England Journal of Medicine.

Prior research into cortical lesions has centered on autopsies of patients with a long history of chronic, progressive MS and has supported the hypothesis that these lesions are not inflammatory. However, the new study, coauthored by Claudia F. Lucchinetti, MD, Professor of Neurology at the Mayo Clinic Rochester in Minnesota, examined biopsies of cortical tissues obtained from white-matter lesions in patients with early-stage MS, all diagnosed within days or weeks of presentation.

“We found that cortical demyelination is common early in MS, and our characterization of the lesion underscored its inflammatory character. Cortical demyelination that occurs close to the onset of MS differs substantially from that seen in chronic MS,” stated Dr. Lucchinetti. “These findings do not support a primary (non-inflammatory) neurodegenerative process during early-stage MS.”

Examining Patients With Early-Stage MS
The collaborative study involved researchers at the Mayo Clinic and co-lead author Richard Ransohoff, MD, Professor of Neurology at the Cleveland Clinic, and included 563 participants who underwent white-matter biopsies, most with the intention of detecting suspected tumors that were later designated as MS.

The median age of the cohort at biopsy was 40.5, and patients were diagnosed with MS according to the McDonald or Poser criteria. Patients with other diseases of the CNS were excluded from the study.

“A separate paper is addressing the details on the clinical spectrum in the cohort,” Dr. Lucchinetti told Neurology Reviews.

Of the 563 eligible patients with MS, only 138 had enough cortex in their biopsies to allow evaluation of the prevalence and character of cortical demyelination.

The investigators used immunohistochemistry to characterize patients’ cortical lesions in four areas—demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and topical association between cortical demyelination and meningeal inflammation. 

Identifying Demyelination and Inflammation
Overall, cortical demyelination was identified in 53 (38%) patients (104 lesions and 222 tissue blocks) of the 138 with sufficient cortex to allow analysis, and cortical demyelination was not present in 85 patients (121 tissue blocks). After undergoing long-term, comprehensive follow-up, 25 patients with cortical demyelination, as well as 33 patients without cortical demyelination, showed definite MS.

Dr. Lucchinetti’s group also looked for CD3+ T cells in 71 lesions from patients with an acceptable amount of representative tissue, and they documented perivascular CD3+ T-cell inflammation in 58 of 71 cortical plaques (82%). “Leukocortical lesions were highly inflammatory,” the researchers noted. “The majority of intracortical and subpial plaques contained perivascular CD3+ and CD8+ T-cell infiltrates.” The investigators also observed macrophage-associated demyelination in 32 of 78 lesions (41%).

Furthermore, in patients with confirmed clinically isolated syndrome (CIS) or MS, there was a strong link between meningeal inflammation and cortical demyelination. “Remarkably, there was a 90% probability that moderate-to-marked meningeal inflammation was topographically associated with cortical demyelination,” the study authors wrote. 

Gray Matter Implications
MS has traditionally been viewed as a disease of the white matter, though in recent years researchers have acknowledged the role of gray matter disease as part of MS progression. However, until now, investigators had not seen strong evidence supporting the idea that the immune system plays an active role in the gray matter of patients with MS. Myelin-laden macrophages, the sign of an active plaque, were not previously observed in cortical tissue, and many researchers have viewed MS as a degenerative rather than inflammatory disease.

In an accompanying editorial, Peter A. Calabresi, MD, Professor of Neurology at the Johns Hopkins School of Medicine in Baltimore, called the findings “provocative” and said that they “provide definitive evidence that inflammatory disease of the gray matter commences early in the pathogenesis of some cases of MS.”

The results enhance the understanding of MS as an inflammatory disease, which might allow researchers to explore different treatment approaches, according to Dr. Calabresi.

“Other studies have led to the concept that the underlying substrate of permanent disability in MS is not inflammation or demyelination, both of which are potentially reversible, but rather neuroaxonal disease,” stated Dr. Calabresi. “The study by Lucchinetti et al suggests that cortical neuronal loss is directly associated with inflammatory demyelination, and therefore early therapeutic efforts to suppress inflammation may be neuroprotective in both gray-matter and white-matter compartments.”   

—Lauren LeBano

Patients with early-stage multiple sclerosis (MS) show cortical demyelinating lesions that are numerous, inflammatory, and strongly linked with meningeal inflammation, according to a study published in the December 8, 2011, New England Journal of Medicine.

Prior research into cortical lesions has centered on autopsies of patients with a long history of chronic, progressive MS and has supported the hypothesis that these lesions are not inflammatory. However, the new study, coauthored by Claudia F. Lucchinetti, MD, Professor of Neurology at the Mayo Clinic Rochester in Minnesota, examined biopsies of cortical tissues obtained from white-matter lesions in patients with early-stage MS, all diagnosed within days or weeks of presentation.

“We found that cortical demyelination is common early in MS, and our characterization of the lesion underscored its inflammatory character. Cortical demyelination that occurs close to the onset of MS differs substantially from that seen in chronic MS,” stated Dr. Lucchinetti. “These findings do not support a primary (non-inflammatory) neurodegenerative process during early-stage MS.”

Examining Patients With Early-Stage MS
The collaborative study involved researchers at the Mayo Clinic and co-lead author Richard Ransohoff, MD, Professor of Neurology at the Cleveland Clinic, and included 563 participants who underwent white-matter biopsies, most with the intention of detecting suspected tumors that were later designated as MS.

The median age of the cohort at biopsy was 40.5, and patients were diagnosed with MS according to the McDonald or Poser criteria. Patients with other diseases of the CNS were excluded from the study.

“A separate paper is addressing the details on the clinical spectrum in the cohort,” Dr. Lucchinetti told Neurology Reviews.

Of the 563 eligible patients with MS, only 138 had enough cortex in their biopsies to allow evaluation of the prevalence and character of cortical demyelination.

The investigators used immunohistochemistry to characterize patients’ cortical lesions in four areas—demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and topical association between cortical demyelination and meningeal inflammation. 

Identifying Demyelination and Inflammation
Overall, cortical demyelination was identified in 53 (38%) patients (104 lesions and 222 tissue blocks) of the 138 with sufficient cortex to allow analysis, and cortical demyelination was not present in 85 patients (121 tissue blocks). After undergoing long-term, comprehensive follow-up, 25 patients with cortical demyelination, as well as 33 patients without cortical demyelination, showed definite MS.

Dr. Lucchinetti’s group also looked for CD3+ T cells in 71 lesions from patients with an acceptable amount of representative tissue, and they documented perivascular CD3+ T-cell inflammation in 58 of 71 cortical plaques (82%). “Leukocortical lesions were highly inflammatory,” the researchers noted. “The majority of intracortical and subpial plaques contained perivascular CD3+ and CD8+ T-cell infiltrates.” The investigators also observed macrophage-associated demyelination in 32 of 78 lesions (41%).

Furthermore, in patients with confirmed clinically isolated syndrome (CIS) or MS, there was a strong link between meningeal inflammation and cortical demyelination. “Remarkably, there was a 90% probability that moderate-to-marked meningeal inflammation was topographically associated with cortical demyelination,” the study authors wrote. 

Gray Matter Implications
MS has traditionally been viewed as a disease of the white matter, though in recent years researchers have acknowledged the role of gray matter disease as part of MS progression. However, until now, investigators had not seen strong evidence supporting the idea that the immune system plays an active role in the gray matter of patients with MS. Myelin-laden macrophages, the sign of an active plaque, were not previously observed in cortical tissue, and many researchers have viewed MS as a degenerative rather than inflammatory disease.

In an accompanying editorial, Peter A. Calabresi, MD, Professor of Neurology at the Johns Hopkins School of Medicine in Baltimore, called the findings “provocative” and said that they “provide definitive evidence that inflammatory disease of the gray matter commences early in the pathogenesis of some cases of MS.”

The results enhance the understanding of MS as an inflammatory disease, which might allow researchers to explore different treatment approaches, according to Dr. Calabresi.

“Other studies have led to the concept that the underlying substrate of permanent disability in MS is not inflammation or demyelination, both of which are potentially reversible, but rather neuroaxonal disease,” stated Dr. Calabresi. “The study by Lucchinetti et al suggests that cortical neuronal loss is directly associated with inflammatory demyelination, and therefore early therapeutic efforts to suppress inflammation may be neuroprotective in both gray-matter and white-matter compartments.”   

—Lauren LeBano

Patients with early-stage multiple sclerosis (MS) show cortical demyelinating lesions that are numerous, inflammatory, and strongly linked with meningeal inflammation, according to a study published in the December 8, 2011, New England Journal of Medicine.

Prior research into cortical lesions has centered on autopsies of patients with a long history of chronic, progressive MS and has supported the hypothesis that these lesions are not inflammatory. However, the new study, coauthored by Claudia F. Lucchinetti, MD, Professor of Neurology at the Mayo Clinic Rochester in Minnesota, examined biopsies of cortical tissues obtained from white-matter lesions in patients with early-stage MS, all diagnosed within days or weeks of presentation.

“We found that cortical demyelination is common early in MS, and our characterization of the lesion underscored its inflammatory character. Cortical demyelination that occurs close to the onset of MS differs substantially from that seen in chronic MS,” stated Dr. Lucchinetti. “These findings do not support a primary (non-inflammatory) neurodegenerative process during early-stage MS.”

Examining Patients With Early-Stage MS
The collaborative study involved researchers at the Mayo Clinic and co-lead author Richard Ransohoff, MD, Professor of Neurology at the Cleveland Clinic, and included 563 participants who underwent white-matter biopsies, most with the intention of detecting suspected tumors that were later designated as MS.

The median age of the cohort at biopsy was 40.5, and patients were diagnosed with MS according to the McDonald or Poser criteria. Patients with other diseases of the CNS were excluded from the study.

“A separate paper is addressing the details on the clinical spectrum in the cohort,” Dr. Lucchinetti told Neurology Reviews.

Of the 563 eligible patients with MS, only 138 had enough cortex in their biopsies to allow evaluation of the prevalence and character of cortical demyelination.

The investigators used immunohistochemistry to characterize patients’ cortical lesions in four areas—demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and topical association between cortical demyelination and meningeal inflammation. 

Identifying Demyelination and Inflammation
Overall, cortical demyelination was identified in 53 (38%) patients (104 lesions and 222 tissue blocks) of the 138 with sufficient cortex to allow analysis, and cortical demyelination was not present in 85 patients (121 tissue blocks). After undergoing long-term, comprehensive follow-up, 25 patients with cortical demyelination, as well as 33 patients without cortical demyelination, showed definite MS.

Dr. Lucchinetti’s group also looked for CD3+ T cells in 71 lesions from patients with an acceptable amount of representative tissue, and they documented perivascular CD3+ T-cell inflammation in 58 of 71 cortical plaques (82%). “Leukocortical lesions were highly inflammatory,” the researchers noted. “The majority of intracortical and subpial plaques contained perivascular CD3+ and CD8+ T-cell infiltrates.” The investigators also observed macrophage-associated demyelination in 32 of 78 lesions (41%).

Furthermore, in patients with confirmed clinically isolated syndrome (CIS) or MS, there was a strong link between meningeal inflammation and cortical demyelination. “Remarkably, there was a 90% probability that moderate-to-marked meningeal inflammation was topographically associated with cortical demyelination,” the study authors wrote. 

Gray Matter Implications
MS has traditionally been viewed as a disease of the white matter, though in recent years researchers have acknowledged the role of gray matter disease as part of MS progression. However, until now, investigators had not seen strong evidence supporting the idea that the immune system plays an active role in the gray matter of patients with MS. Myelin-laden macrophages, the sign of an active plaque, were not previously observed in cortical tissue, and many researchers have viewed MS as a degenerative rather than inflammatory disease.

In an accompanying editorial, Peter A. Calabresi, MD, Professor of Neurology at the Johns Hopkins School of Medicine in Baltimore, called the findings “provocative” and said that they “provide definitive evidence that inflammatory disease of the gray matter commences early in the pathogenesis of some cases of MS.”

The results enhance the understanding of MS as an inflammatory disease, which might allow researchers to explore different treatment approaches, according to Dr. Calabresi.

“Other studies have led to the concept that the underlying substrate of permanent disability in MS is not inflammation or demyelination, both of which are potentially reversible, but rather neuroaxonal disease,” stated Dr. Calabresi. “The study by Lucchinetti et al suggests that cortical neuronal loss is directly associated with inflammatory demyelination, and therefore early therapeutic efforts to suppress inflammation may be neuroprotective in both gray-matter and white-matter compartments.”   

—Lauren LeBano

Demographic and Clinical Factors Influence Survival of Patients With Parkinson’s Disease
Clinical conditions such as dementia and demographic factors such as race, sex, and age influence the survival rates of patients with Parkinson’s disease, according to research published in the January 2 issue of Archives of Neurology.

To determine the life expectancy of patients with Parkinson’s disease in the United States and identify factors that influence survival, Allison W. Willis, MD, of the Department of Neurology at the Washington University School of Medicine in St. Louis, and colleagues conducted a retrospective cohort study of 138,728 Medicare beneficiaries with incident Parkinson’s disease. Patients were 65 and older, and the population included 65,423 men and 73,305 women. The researchers identified the patients in 2002 and followed up through 2008.

The main outcome measures were confounder-adjusted six-year risk of death as influenced by three groups of factors, including race, sex, and age at diagnosis; geography and environmental factors; and clinical conditions. Dr. Willis examined hospitalization diagnoses in patients with terminal Parkinson’s disease and compared disease mortality with that of other common diseases.

Sixty-four percent of patients with Parkinson’s disease died during the six-year study, and the authors found that “sex and race significantly predicted survival.” Women with Parkinson’s disease had a 26% lower adjusted risk of death than men. African Americans and whites had the two highest crude death rates at 66.4% and 64.6%, respectively. Hispanics had a lower death rate (ie, 55.4%), and Asians had the lowest death rate (50.8%). Survival decreased with age.

Dementia was diagnosed in 69.6% of cases and was associated with a greater likelihood of death. Patients with Parkinson’s disease and dementia had a 28.1% survival rate, while patients without dementia had a 53.9% survival rate. Patients with dementia and Parkinson’s disease were 72% more likely to die during the study, and dementia had the strongest effect on age-adjusted survival among the variables studied, according to the authors.

Survival rates were similar across states, between regions of the country, and by rural or urban classification. However, patients with Parkinson’s disease who lived in urban areas and areas of high industrial metal emissions had a slightly higher adjusted risk of death (19%). Dr. Willis and her colleagues concluded that more research was needed to understand whether environmental exposures influence survival among patients with Parkinson’s disease.
Willis AW, Schootman M, Kung N, et al. Predictors of survival in patients with Parkinson disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Latent Epstein-Barr Virus May Activate Innate Immune Responses in the MS Brain
Latent Epstein-Barr virus (EBV) infection may contribute to neuroinflammation in patients with multiple sclerosis (MS), according to research published in the January 3 issue of Neurology.

A team led by J. S. Tzartos, DPhil, of the Department of Neuropathology, John Radcliffe Hospital, University of Oxford, United Kingdom, studied whether the activation of innate immune responses was associated with the presence of EBV in brains afflicted with MS. The group used immunohistochemistry to analyze 10 samples of white matter postmortem MS and 11 samples of control tissue for the expression of the proinflammatory cytokine interferon α (IFNα). The researchers also analyzed the samples for EBV using EBV-encoded RNA (EBER) in situ hybridization.

Dr. Tzartos and colleagues found overexpression of IFNα in active areas of white matter MS lesions, but not in inactive MS lesions, normal-appearing white matter, or normal brains. The team also found EBERs in areas where IFNα was overexpressed in active MS lesions. EBER+ cells were present in samples taken from CNS lymphoma and stroke cases, but not in other control brains. After transfecting EBERs into human embryonic kidney cells, the researchers found that the former elicited IFNα production in vitro.

“As we found EBER+ cells not only in white matter areas of these active MS lesions, but also CNS lymphoma and two cases of stroke, we conclude that the presence of EBV may not be unique to the MS brain, in contrast to previous findings,” wrote Dr. Tzartos. “Thus, our study casts new light on mechanistic interactions of viral RNAs and innate immune activation in the CNS, and may highlight the propensity of latent viral infections to contribute to neuroinflammation in the CNS, not only in MS, but also in other neuroinflammatory diseases.”

Dr. Tzartos’s findings “revitalize a debate that was heading toward a negative conclusion, that is, EBV-infected B cells are a rare and coincidental finding in MS brains,” wrote Jan D. Lünemann, MD, of the University of Zürich, in an accompanying editorial. An accumulation of EBV-infected B cells in inflammatory CNS lesions, which are rich in B cells, may represent a bystander phenomenon, but “bystanders do not necessarily remain silent and innocent,” wrote Dr. Lünemann.
Tzartos JS, Khan G, Vossenkamper A, et al. Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology. 2012;78(1):15–23.
Lünemann JD, Epstein–Barr virus in multiple sclerosis. Neurology. 2012;78(1):11–12.

High Adiponectin Levels May Increase Dementia Risk in Women
Women with elevated plasma adiponectin levels may have an increased risk of developing both all-cause dementia and Alzheimer’s disease, researchers reported in the January 2 online issue of Archives of Neurology.

Thomas M. van Himbergen, PhD, a postdoctoral associate at the Lipid Metabolism Laboratory at Tufts University in Boston, and colleagues examined biomarkers for glucose homeostasis (ie, adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (ie, high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 levels) in a prospective cohort study that included 840 dementia-free participants in the Framingham Heart Study. The participants, 541 of whom were women, had a median age of 76, and the researchers measured subjects’ sera for biomarkers at the 19th biennial examination (1985 to 1988).

During the mean 13-year follow-up period for development of Alzheimer’s disease and all-cause dementia, 159 cases of dementia were identified, including 125 cases of Alzheimer’s disease. To evaluate which biomarkers may contribute to disease development, the researchers used sex-pooled and sex-specific Multivariable Cox Proportional Hazards models to control for other dementia risk factors such as age, education, APOE e4 allele status, plasma docosahexaenoic acid levels, weight change, and BMI.

Plasma insulin, glucose, and glycated albumin levels as well as the inflammatory marker lipoprotein-associated phospholipase A2 were not linked with Alzheimer’s disease or all-cause dementia. Although high-sensitivity C-reactive protein initially seemed to be associated with a lower risk of Alzheimer’s disease and dementia, adjustment for the APOE e4 allele and other factors revealed that the association was not significant. The investigators identified adiponectin as the only factor associated with a higher risk of all-cause dementia and Alzheimer’s disease in women.

Furthermore, women with baseline adiponectin levels greater than the sex-specific median showed a higher risk of all-cause dementia, compared to women with adiponectin values less than the median, even after adjustment for other risk factors.

“It is well established that insulin signaling is dysfunctional in the brains of patients with Alzheimer’s disease, and since adiponectin enhances insulin sensitivity, one would also expect beneficial actions protecting against cognitive decline,” Dr. van Himbergen’s group noted. “Our data, however, indicated that elevated adiponectin level was associated with an increased risk of dementia and Alzheimer’s disease in women.”
van Himbergen TM, Beiser AS, Ai M, et al. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Demographic and Clinical Factors Influence Survival of Patients With Parkinson’s Disease
Clinical conditions such as dementia and demographic factors such as race, sex, and age influence the survival rates of patients with Parkinson’s disease, according to research published in the January 2 issue of Archives of Neurology.

To determine the life expectancy of patients with Parkinson’s disease in the United States and identify factors that influence survival, Allison W. Willis, MD, of the Department of Neurology at the Washington University School of Medicine in St. Louis, and colleagues conducted a retrospective cohort study of 138,728 Medicare beneficiaries with incident Parkinson’s disease. Patients were 65 and older, and the population included 65,423 men and 73,305 women. The researchers identified the patients in 2002 and followed up through 2008.

The main outcome measures were confounder-adjusted six-year risk of death as influenced by three groups of factors, including race, sex, and age at diagnosis; geography and environmental factors; and clinical conditions. Dr. Willis examined hospitalization diagnoses in patients with terminal Parkinson’s disease and compared disease mortality with that of other common diseases.

Sixty-four percent of patients with Parkinson’s disease died during the six-year study, and the authors found that “sex and race significantly predicted survival.” Women with Parkinson’s disease had a 26% lower adjusted risk of death than men. African Americans and whites had the two highest crude death rates at 66.4% and 64.6%, respectively. Hispanics had a lower death rate (ie, 55.4%), and Asians had the lowest death rate (50.8%). Survival decreased with age.

Dementia was diagnosed in 69.6% of cases and was associated with a greater likelihood of death. Patients with Parkinson’s disease and dementia had a 28.1% survival rate, while patients without dementia had a 53.9% survival rate. Patients with dementia and Parkinson’s disease were 72% more likely to die during the study, and dementia had the strongest effect on age-adjusted survival among the variables studied, according to the authors.

Survival rates were similar across states, between regions of the country, and by rural or urban classification. However, patients with Parkinson’s disease who lived in urban areas and areas of high industrial metal emissions had a slightly higher adjusted risk of death (19%). Dr. Willis and her colleagues concluded that more research was needed to understand whether environmental exposures influence survival among patients with Parkinson’s disease.
Willis AW, Schootman M, Kung N, et al. Predictors of survival in patients with Parkinson disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Latent Epstein-Barr Virus May Activate Innate Immune Responses in the MS Brain
Latent Epstein-Barr virus (EBV) infection may contribute to neuroinflammation in patients with multiple sclerosis (MS), according to research published in the January 3 issue of Neurology.

A team led by J. S. Tzartos, DPhil, of the Department of Neuropathology, John Radcliffe Hospital, University of Oxford, United Kingdom, studied whether the activation of innate immune responses was associated with the presence of EBV in brains afflicted with MS. The group used immunohistochemistry to analyze 10 samples of white matter postmortem MS and 11 samples of control tissue for the expression of the proinflammatory cytokine interferon α (IFNα). The researchers also analyzed the samples for EBV using EBV-encoded RNA (EBER) in situ hybridization.

Dr. Tzartos and colleagues found overexpression of IFNα in active areas of white matter MS lesions, but not in inactive MS lesions, normal-appearing white matter, or normal brains. The team also found EBERs in areas where IFNα was overexpressed in active MS lesions. EBER+ cells were present in samples taken from CNS lymphoma and stroke cases, but not in other control brains. After transfecting EBERs into human embryonic kidney cells, the researchers found that the former elicited IFNα production in vitro.

“As we found EBER+ cells not only in white matter areas of these active MS lesions, but also CNS lymphoma and two cases of stroke, we conclude that the presence of EBV may not be unique to the MS brain, in contrast to previous findings,” wrote Dr. Tzartos. “Thus, our study casts new light on mechanistic interactions of viral RNAs and innate immune activation in the CNS, and may highlight the propensity of latent viral infections to contribute to neuroinflammation in the CNS, not only in MS, but also in other neuroinflammatory diseases.”

Dr. Tzartos’s findings “revitalize a debate that was heading toward a negative conclusion, that is, EBV-infected B cells are a rare and coincidental finding in MS brains,” wrote Jan D. Lünemann, MD, of the University of Zürich, in an accompanying editorial. An accumulation of EBV-infected B cells in inflammatory CNS lesions, which are rich in B cells, may represent a bystander phenomenon, but “bystanders do not necessarily remain silent and innocent,” wrote Dr. Lünemann.
Tzartos JS, Khan G, Vossenkamper A, et al. Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology. 2012;78(1):15–23.
Lünemann JD, Epstein–Barr virus in multiple sclerosis. Neurology. 2012;78(1):11–12.

High Adiponectin Levels May Increase Dementia Risk in Women
Women with elevated plasma adiponectin levels may have an increased risk of developing both all-cause dementia and Alzheimer’s disease, researchers reported in the January 2 online issue of Archives of Neurology.

Thomas M. van Himbergen, PhD, a postdoctoral associate at the Lipid Metabolism Laboratory at Tufts University in Boston, and colleagues examined biomarkers for glucose homeostasis (ie, adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (ie, high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 levels) in a prospective cohort study that included 840 dementia-free participants in the Framingham Heart Study. The participants, 541 of whom were women, had a median age of 76, and the researchers measured subjects’ sera for biomarkers at the 19th biennial examination (1985 to 1988).

During the mean 13-year follow-up period for development of Alzheimer’s disease and all-cause dementia, 159 cases of dementia were identified, including 125 cases of Alzheimer’s disease. To evaluate which biomarkers may contribute to disease development, the researchers used sex-pooled and sex-specific Multivariable Cox Proportional Hazards models to control for other dementia risk factors such as age, education, APOE e4 allele status, plasma docosahexaenoic acid levels, weight change, and BMI.

Plasma insulin, glucose, and glycated albumin levels as well as the inflammatory marker lipoprotein-associated phospholipase A2 were not linked with Alzheimer’s disease or all-cause dementia. Although high-sensitivity C-reactive protein initially seemed to be associated with a lower risk of Alzheimer’s disease and dementia, adjustment for the APOE e4 allele and other factors revealed that the association was not significant. The investigators identified adiponectin as the only factor associated with a higher risk of all-cause dementia and Alzheimer’s disease in women.

Furthermore, women with baseline adiponectin levels greater than the sex-specific median showed a higher risk of all-cause dementia, compared to women with adiponectin values less than the median, even after adjustment for other risk factors.

“It is well established that insulin signaling is dysfunctional in the brains of patients with Alzheimer’s disease, and since adiponectin enhances insulin sensitivity, one would also expect beneficial actions protecting against cognitive decline,” Dr. van Himbergen’s group noted. “Our data, however, indicated that elevated adiponectin level was associated with an increased risk of dementia and Alzheimer’s disease in women.”
van Himbergen TM, Beiser AS, Ai M, et al. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Demographic and Clinical Factors Influence Survival of Patients With Parkinson’s Disease
Clinical conditions such as dementia and demographic factors such as race, sex, and age influence the survival rates of patients with Parkinson’s disease, according to research published in the January 2 issue of Archives of Neurology.

To determine the life expectancy of patients with Parkinson’s disease in the United States and identify factors that influence survival, Allison W. Willis, MD, of the Department of Neurology at the Washington University School of Medicine in St. Louis, and colleagues conducted a retrospective cohort study of 138,728 Medicare beneficiaries with incident Parkinson’s disease. Patients were 65 and older, and the population included 65,423 men and 73,305 women. The researchers identified the patients in 2002 and followed up through 2008.

The main outcome measures were confounder-adjusted six-year risk of death as influenced by three groups of factors, including race, sex, and age at diagnosis; geography and environmental factors; and clinical conditions. Dr. Willis examined hospitalization diagnoses in patients with terminal Parkinson’s disease and compared disease mortality with that of other common diseases.

Sixty-four percent of patients with Parkinson’s disease died during the six-year study, and the authors found that “sex and race significantly predicted survival.” Women with Parkinson’s disease had a 26% lower adjusted risk of death than men. African Americans and whites had the two highest crude death rates at 66.4% and 64.6%, respectively. Hispanics had a lower death rate (ie, 55.4%), and Asians had the lowest death rate (50.8%). Survival decreased with age.

Dementia was diagnosed in 69.6% of cases and was associated with a greater likelihood of death. Patients with Parkinson’s disease and dementia had a 28.1% survival rate, while patients without dementia had a 53.9% survival rate. Patients with dementia and Parkinson’s disease were 72% more likely to die during the study, and dementia had the strongest effect on age-adjusted survival among the variables studied, according to the authors.

Survival rates were similar across states, between regions of the country, and by rural or urban classification. However, patients with Parkinson’s disease who lived in urban areas and areas of high industrial metal emissions had a slightly higher adjusted risk of death (19%). Dr. Willis and her colleagues concluded that more research was needed to understand whether environmental exposures influence survival among patients with Parkinson’s disease.
Willis AW, Schootman M, Kung N, et al. Predictors of survival in patients with Parkinson disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Latent Epstein-Barr Virus May Activate Innate Immune Responses in the MS Brain
Latent Epstein-Barr virus (EBV) infection may contribute to neuroinflammation in patients with multiple sclerosis (MS), according to research published in the January 3 issue of Neurology.

A team led by J. S. Tzartos, DPhil, of the Department of Neuropathology, John Radcliffe Hospital, University of Oxford, United Kingdom, studied whether the activation of innate immune responses was associated with the presence of EBV in brains afflicted with MS. The group used immunohistochemistry to analyze 10 samples of white matter postmortem MS and 11 samples of control tissue for the expression of the proinflammatory cytokine interferon α (IFNα). The researchers also analyzed the samples for EBV using EBV-encoded RNA (EBER) in situ hybridization.

Dr. Tzartos and colleagues found overexpression of IFNα in active areas of white matter MS lesions, but not in inactive MS lesions, normal-appearing white matter, or normal brains. The team also found EBERs in areas where IFNα was overexpressed in active MS lesions. EBER+ cells were present in samples taken from CNS lymphoma and stroke cases, but not in other control brains. After transfecting EBERs into human embryonic kidney cells, the researchers found that the former elicited IFNα production in vitro.

“As we found EBER+ cells not only in white matter areas of these active MS lesions, but also CNS lymphoma and two cases of stroke, we conclude that the presence of EBV may not be unique to the MS brain, in contrast to previous findings,” wrote Dr. Tzartos. “Thus, our study casts new light on mechanistic interactions of viral RNAs and innate immune activation in the CNS, and may highlight the propensity of latent viral infections to contribute to neuroinflammation in the CNS, not only in MS, but also in other neuroinflammatory diseases.”

Dr. Tzartos’s findings “revitalize a debate that was heading toward a negative conclusion, that is, EBV-infected B cells are a rare and coincidental finding in MS brains,” wrote Jan D. Lünemann, MD, of the University of Zürich, in an accompanying editorial. An accumulation of EBV-infected B cells in inflammatory CNS lesions, which are rich in B cells, may represent a bystander phenomenon, but “bystanders do not necessarily remain silent and innocent,” wrote Dr. Lünemann.
Tzartos JS, Khan G, Vossenkamper A, et al. Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology. 2012;78(1):15–23.
Lünemann JD, Epstein–Barr virus in multiple sclerosis. Neurology. 2012;78(1):11–12.

High Adiponectin Levels May Increase Dementia Risk in Women
Women with elevated plasma adiponectin levels may have an increased risk of developing both all-cause dementia and Alzheimer’s disease, researchers reported in the January 2 online issue of Archives of Neurology.

Thomas M. van Himbergen, PhD, a postdoctoral associate at the Lipid Metabolism Laboratory at Tufts University in Boston, and colleagues examined biomarkers for glucose homeostasis (ie, adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (ie, high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 levels) in a prospective cohort study that included 840 dementia-free participants in the Framingham Heart Study. The participants, 541 of whom were women, had a median age of 76, and the researchers measured subjects’ sera for biomarkers at the 19th biennial examination (1985 to 1988).

During the mean 13-year follow-up period for development of Alzheimer’s disease and all-cause dementia, 159 cases of dementia were identified, including 125 cases of Alzheimer’s disease. To evaluate which biomarkers may contribute to disease development, the researchers used sex-pooled and sex-specific Multivariable Cox Proportional Hazards models to control for other dementia risk factors such as age, education, APOE e4 allele status, plasma docosahexaenoic acid levels, weight change, and BMI.

Plasma insulin, glucose, and glycated albumin levels as well as the inflammatory marker lipoprotein-associated phospholipase A2 were not linked with Alzheimer’s disease or all-cause dementia. Although high-sensitivity C-reactive protein initially seemed to be associated with a lower risk of Alzheimer’s disease and dementia, adjustment for the APOE e4 allele and other factors revealed that the association was not significant. The investigators identified adiponectin as the only factor associated with a higher risk of all-cause dementia and Alzheimer’s disease in women.

Furthermore, women with baseline adiponectin levels greater than the sex-specific median showed a higher risk of all-cause dementia, compared to women with adiponectin values less than the median, even after adjustment for other risk factors.

“It is well established that insulin signaling is dysfunctional in the brains of patients with Alzheimer’s disease, and since adiponectin enhances insulin sensitivity, one would also expect beneficial actions protecting against cognitive decline,” Dr. van Himbergen’s group noted. “Our data, however, indicated that elevated adiponectin level was associated with an increased risk of dementia and Alzheimer’s disease in women.”
van Himbergen TM, Beiser AS, Ai M, et al. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease. Arch Neurol. 2012 Jan 2; [Epub ahead of print].

Researchers will prospectively assess clinical information, MRI data, blood biomarkers, and genetic variables to evaluate risk factors that affect MS disease progression.

AMSTERDAM—Researchers have established the Serial Unified Multicenter Multiple Sclerosis (MS) Investigation (SUMMIT) international consortium to prospectively evaluate risk factors that affect disease progression in a large, multinational cohort of patients with MS, according to a presentation at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

“Such longitudinal studies will be needed to understand disease progression in the modern era of treatment,” Howard L. Weiner, MD, Professor of Neurology at Harvard Medical School in Boston, and his colleagues noted.

Evaluating Disease Progression Factors
To predict factors affecting disease progression, Dr. Weiner’s team will assess clinical information, MRI data, blood biomarkers, and genetic variables from 1,500 patients with MS enrolled at international MS Centers in Boston; San Francisco; Basel, Switzerland; and Amsterdam. Each European site will contribute 250 patients to the SUMMIT study, while each US site will contribute 500 patients.

“We hope to present initial results at next year’s ECTRIMS, and we hope the SUMMIT will follow patients for at least a decade,” Dr. Weiner told Neurology Reviews.

Data collection for the study began in 2011, and the sites will maintain communication throughout the process with conference calls and bi-annual meetings.

Each year, the researchers will collect standardized clinical data on all patients, including medical and family history, the date and features of disease onset, relapse details, and current and historical treatments. The investigators will also analyze results obtained from the Symbol Digit Modalities Test, the Ambulation Index, and the Expanded Disability Status Scale (EDSS).

In addition, Dr. Weiner’s team developed a standardized questionnaire to obtain information about patient demographics, as well as epidemiologic factors such as alcohol and smoking history, diet and allergies, vitamin D intake, and vaccination history. To evaluate influences specific to females, the study will obtain data on menses onset, pregnancy, breast-feeding, fertility treatments, menopause, and hormone medications. 

Biologic samples from all participants will be collected to assess antigen microarrays, RNA microarrays, vitamin D levels, and serum biomarkers, and MRI will be used to measure T2 lesion volume, normalized brain volume, and gadolinium-enhancing lesions. The researchers added that, “A genome-wide meta-analysis for single nucleotide polymorphisms that influence clinical and MRI outcome measures is planned.”

Current Progress and Future Outcomes
Thus far, the SUMMIT study has made some progress toward its goals. The team obtained institutional review board (human studies) approval, established a data collection platform and uniform collection forms and fields, and created working groups.

The research group anticipates using statistical methodologies and computerized analysis software to analyze univariate and multivariate predictors of disease progression. “We think that MRI, biomarkers, and clinical features of the patients will be the most influential,” Dr. Weiner commented.

The investigators expect to add more collaborative partners to the study in the future. Dr. Weiner explained, “Once the SUMMIT structure has been firmly established and is operational, which should take approximately one more year, we will be talking to other MS centers to see if any are interested in participating and how to provide for long-term funding.

“We hope the clinical implications will relate to understanding the course of disease in individual patients and how to modify factors that will affect long-term progression,” he concluded.                                 

Researchers will prospectively assess clinical information, MRI data, blood biomarkers, and genetic variables to evaluate risk factors that affect MS disease progression.

AMSTERDAM—Researchers have established the Serial Unified Multicenter Multiple Sclerosis (MS) Investigation (SUMMIT) international consortium to prospectively evaluate risk factors that affect disease progression in a large, multinational cohort of patients with MS, according to a presentation at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

“Such longitudinal studies will be needed to understand disease progression in the modern era of treatment,” Howard L. Weiner, MD, Professor of Neurology at Harvard Medical School in Boston, and his colleagues noted.

Evaluating Disease Progression Factors
To predict factors affecting disease progression, Dr. Weiner’s team will assess clinical information, MRI data, blood biomarkers, and genetic variables from 1,500 patients with MS enrolled at international MS Centers in Boston; San Francisco; Basel, Switzerland; and Amsterdam. Each European site will contribute 250 patients to the SUMMIT study, while each US site will contribute 500 patients.

“We hope to present initial results at next year’s ECTRIMS, and we hope the SUMMIT will follow patients for at least a decade,” Dr. Weiner told Neurology Reviews.

Data collection for the study began in 2011, and the sites will maintain communication throughout the process with conference calls and bi-annual meetings.

Each year, the researchers will collect standardized clinical data on all patients, including medical and family history, the date and features of disease onset, relapse details, and current and historical treatments. The investigators will also analyze results obtained from the Symbol Digit Modalities Test, the Ambulation Index, and the Expanded Disability Status Scale (EDSS).

In addition, Dr. Weiner’s team developed a standardized questionnaire to obtain information about patient demographics, as well as epidemiologic factors such as alcohol and smoking history, diet and allergies, vitamin D intake, and vaccination history. To evaluate influences specific to females, the study will obtain data on menses onset, pregnancy, breast-feeding, fertility treatments, menopause, and hormone medications. 

Biologic samples from all participants will be collected to assess antigen microarrays, RNA microarrays, vitamin D levels, and serum biomarkers, and MRI will be used to measure T2 lesion volume, normalized brain volume, and gadolinium-enhancing lesions. The researchers added that, “A genome-wide meta-analysis for single nucleotide polymorphisms that influence clinical and MRI outcome measures is planned.”

Current Progress and Future Outcomes
Thus far, the SUMMIT study has made some progress toward its goals. The team obtained institutional review board (human studies) approval, established a data collection platform and uniform collection forms and fields, and created working groups.

The research group anticipates using statistical methodologies and computerized analysis software to analyze univariate and multivariate predictors of disease progression. “We think that MRI, biomarkers, and clinical features of the patients will be the most influential,” Dr. Weiner commented.

The investigators expect to add more collaborative partners to the study in the future. Dr. Weiner explained, “Once the SUMMIT structure has been firmly established and is operational, which should take approximately one more year, we will be talking to other MS centers to see if any are interested in participating and how to provide for long-term funding.

“We hope the clinical implications will relate to understanding the course of disease in individual patients and how to modify factors that will affect long-term progression,” he concluded.                                 

Researchers will prospectively assess clinical information, MRI data, blood biomarkers, and genetic variables to evaluate risk factors that affect MS disease progression.

AMSTERDAM—Researchers have established the Serial Unified Multicenter Multiple Sclerosis (MS) Investigation (SUMMIT) international consortium to prospectively evaluate risk factors that affect disease progression in a large, multinational cohort of patients with MS, according to a presentation at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

“Such longitudinal studies will be needed to understand disease progression in the modern era of treatment,” Howard L. Weiner, MD, Professor of Neurology at Harvard Medical School in Boston, and his colleagues noted.

Evaluating Disease Progression Factors
To predict factors affecting disease progression, Dr. Weiner’s team will assess clinical information, MRI data, blood biomarkers, and genetic variables from 1,500 patients with MS enrolled at international MS Centers in Boston; San Francisco; Basel, Switzerland; and Amsterdam. Each European site will contribute 250 patients to the SUMMIT study, while each US site will contribute 500 patients.

“We hope to present initial results at next year’s ECTRIMS, and we hope the SUMMIT will follow patients for at least a decade,” Dr. Weiner told Neurology Reviews.

Data collection for the study began in 2011, and the sites will maintain communication throughout the process with conference calls and bi-annual meetings.

Each year, the researchers will collect standardized clinical data on all patients, including medical and family history, the date and features of disease onset, relapse details, and current and historical treatments. The investigators will also analyze results obtained from the Symbol Digit Modalities Test, the Ambulation Index, and the Expanded Disability Status Scale (EDSS).

In addition, Dr. Weiner’s team developed a standardized questionnaire to obtain information about patient demographics, as well as epidemiologic factors such as alcohol and smoking history, diet and allergies, vitamin D intake, and vaccination history. To evaluate influences specific to females, the study will obtain data on menses onset, pregnancy, breast-feeding, fertility treatments, menopause, and hormone medications. 

Biologic samples from all participants will be collected to assess antigen microarrays, RNA microarrays, vitamin D levels, and serum biomarkers, and MRI will be used to measure T2 lesion volume, normalized brain volume, and gadolinium-enhancing lesions. The researchers added that, “A genome-wide meta-analysis for single nucleotide polymorphisms that influence clinical and MRI outcome measures is planned.”

Current Progress and Future Outcomes
Thus far, the SUMMIT study has made some progress toward its goals. The team obtained institutional review board (human studies) approval, established a data collection platform and uniform collection forms and fields, and created working groups.

The research group anticipates using statistical methodologies and computerized analysis software to analyze univariate and multivariate predictors of disease progression. “We think that MRI, biomarkers, and clinical features of the patients will be the most influential,” Dr. Weiner commented.

The investigators expect to add more collaborative partners to the study in the future. Dr. Weiner explained, “Once the SUMMIT structure has been firmly established and is operational, which should take approximately one more year, we will be talking to other MS centers to see if any are interested in participating and how to provide for long-term funding.

“We hope the clinical implications will relate to understanding the course of disease in individual patients and how to modify factors that will affect long-term progression,” he concluded.                                 

Researchers conduct a retrospective study to determine whether children with MS can be diagnosed after an initial event and MRI.

SAVANNAH, GA—Applying the 2010 Revised McDonald Diagnostic Criteria for Multiple Sclerosis (MS) could have led to an earlier diagnosis among some pediatric demyelinating patients, according to research presented at the 40th National Meeting of the Child Neurology Society.

“Revised 2010 MS diagnostic criteria now allow a single brain MRI with more than one T2 lesion in at least two regions and one enhancing lesion to fulfill dissemination in time and space,” noted Thitiwan Simasathien, MD, Child Neurology Fellow, and Jayne M. Ness, MD, PhD, Associate Professor, both at the University of Alabama in Birmingham. “However, this streamlined diagnosis of MS had not been validated in pediatric demyelinating patients.”

Evaluating the 2010 MS Diagnostic Criteria
The investigators conducted a retrospective chart review evaluating the utility of the 2010 MS diagnostic criteria in a cohort of 42 pediatric patients with MS. All participants (70% female, 40% African American) were younger than 18 and presented with clinically isolated syndrome (CIS) from 1998 to 2008, with a mean onset age of 13.1. Of the patients, none were documented with encephalopathy, six presented with optic neuritis (five unilateral, one bilateral), and 36 presented with pyramidal or brainstem symptoms.

The researchers determined whether the first MRI conducted on these patients fulfilled 2010 MS diagnostic criteria, finding that 40% of the cohort (17/42) showed dissemination in time and space on their initial MRI. Drs. Simasathien and Ness noted no differences in age, race, or sex between patients who met the 2010 diagnostic criteria and those who did not.

If the 2010 criteria had been applied to the participants at the time of their initial CIS presentation, some patients could have received an earlier diagnosis of MS and potentially could have begun disease-modifying therapy sooner, the investigators concluded. Although the findings of the retrospective study show promise, “Further study is necessary to assess the validity of these criteria in pediatric demyelinating patients,” the researchers stated.

Dr. Ness told Neurology Reviews, “It will be critical to assess whether the streamlined 2010 McDonald criteria have appropriate specificity to ensure that children with self-limited demyelinating syndromes—such as acute disseminated encephalomyelitis or conditions requiring different treatment approaches, such as neuromyelitis optica—are not incorrectly diagnosed with MS.”                     

Researchers conduct a retrospective study to determine whether children with MS can be diagnosed after an initial event and MRI.

SAVANNAH, GA—Applying the 2010 Revised McDonald Diagnostic Criteria for Multiple Sclerosis (MS) could have led to an earlier diagnosis among some pediatric demyelinating patients, according to research presented at the 40th National Meeting of the Child Neurology Society.

“Revised 2010 MS diagnostic criteria now allow a single brain MRI with more than one T2 lesion in at least two regions and one enhancing lesion to fulfill dissemination in time and space,” noted Thitiwan Simasathien, MD, Child Neurology Fellow, and Jayne M. Ness, MD, PhD, Associate Professor, both at the University of Alabama in Birmingham. “However, this streamlined diagnosis of MS had not been validated in pediatric demyelinating patients.”

Evaluating the 2010 MS Diagnostic Criteria
The investigators conducted a retrospective chart review evaluating the utility of the 2010 MS diagnostic criteria in a cohort of 42 pediatric patients with MS. All participants (70% female, 40% African American) were younger than 18 and presented with clinically isolated syndrome (CIS) from 1998 to 2008, with a mean onset age of 13.1. Of the patients, none were documented with encephalopathy, six presented with optic neuritis (five unilateral, one bilateral), and 36 presented with pyramidal or brainstem symptoms.

The researchers determined whether the first MRI conducted on these patients fulfilled 2010 MS diagnostic criteria, finding that 40% of the cohort (17/42) showed dissemination in time and space on their initial MRI. Drs. Simasathien and Ness noted no differences in age, race, or sex between patients who met the 2010 diagnostic criteria and those who did not.

If the 2010 criteria had been applied to the participants at the time of their initial CIS presentation, some patients could have received an earlier diagnosis of MS and potentially could have begun disease-modifying therapy sooner, the investigators concluded. Although the findings of the retrospective study show promise, “Further study is necessary to assess the validity of these criteria in pediatric demyelinating patients,” the researchers stated.

Dr. Ness told Neurology Reviews, “It will be critical to assess whether the streamlined 2010 McDonald criteria have appropriate specificity to ensure that children with self-limited demyelinating syndromes—such as acute disseminated encephalomyelitis or conditions requiring different treatment approaches, such as neuromyelitis optica—are not incorrectly diagnosed with MS.”                     

Researchers conduct a retrospective study to determine whether children with MS can be diagnosed after an initial event and MRI.

SAVANNAH, GA—Applying the 2010 Revised McDonald Diagnostic Criteria for Multiple Sclerosis (MS) could have led to an earlier diagnosis among some pediatric demyelinating patients, according to research presented at the 40th National Meeting of the Child Neurology Society.

“Revised 2010 MS diagnostic criteria now allow a single brain MRI with more than one T2 lesion in at least two regions and one enhancing lesion to fulfill dissemination in time and space,” noted Thitiwan Simasathien, MD, Child Neurology Fellow, and Jayne M. Ness, MD, PhD, Associate Professor, both at the University of Alabama in Birmingham. “However, this streamlined diagnosis of MS had not been validated in pediatric demyelinating patients.”

Evaluating the 2010 MS Diagnostic Criteria
The investigators conducted a retrospective chart review evaluating the utility of the 2010 MS diagnostic criteria in a cohort of 42 pediatric patients with MS. All participants (70% female, 40% African American) were younger than 18 and presented with clinically isolated syndrome (CIS) from 1998 to 2008, with a mean onset age of 13.1. Of the patients, none were documented with encephalopathy, six presented with optic neuritis (five unilateral, one bilateral), and 36 presented with pyramidal or brainstem symptoms.

The researchers determined whether the first MRI conducted on these patients fulfilled 2010 MS diagnostic criteria, finding that 40% of the cohort (17/42) showed dissemination in time and space on their initial MRI. Drs. Simasathien and Ness noted no differences in age, race, or sex between patients who met the 2010 diagnostic criteria and those who did not.

If the 2010 criteria had been applied to the participants at the time of their initial CIS presentation, some patients could have received an earlier diagnosis of MS and potentially could have begun disease-modifying therapy sooner, the investigators concluded. Although the findings of the retrospective study show promise, “Further study is necessary to assess the validity of these criteria in pediatric demyelinating patients,” the researchers stated.

Dr. Ness told Neurology Reviews, “It will be critical to assess whether the streamlined 2010 McDonald criteria have appropriate specificity to ensure that children with self-limited demyelinating syndromes—such as acute disseminated encephalomyelitis or conditions requiring different treatment approaches, such as neuromyelitis optica—are not incorrectly diagnosed with MS.”                     

Two surveys of American multiple sclerosis (MS) specialists reveal a general consensus of practice patterns in primary and secondary progressive MS, relapsing-remitting MS, and clinically isolated syndrome.

AMSTERDAM—Neurologists from multiple sclerosis (MS) treatment centers across the US generally agree on the use of spinal MRI or lumbar puncture for diagnosis of the disease, but more research regarding treatment responses and therapies is needed, according to the results of two studies presented at the 5th Joint Triennial Congress of the European Committee for Treatment and Research in Multiple Sclerosis/Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).

“The current research effort was conducted with the goal of gaining an understanding of the current diagnostic and treatment practices of MS specialists at US MS treatment centers,” the investigators stated. The surveys were designed to determine the influence and use of various diagnostic and clinical parameters in clinical decisions pertaining to disease-modifying therapy initiation, switching, and selection.

The team of researchers, led by Omar A. Khan, MD, from the Department of Neurology at Wayne State University in Detroit, and Carlo Tornatore, MD, from the Department of Neurology at Georgetown University in Washington, DC, invited neurologists from 207 MS treatment centers to participate in the study. Two web-based surveys evaluating practice patterns for various forms of MS were developed and distributed to specialists; 75 specialists completed the first survey, and 71 of those completed the second survey.

CIS, RIS, and RRMS
The investigators presented participating MS specialists with patient scenarios regarding clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and radiologically isolated syndrome (RIS). Regarding CIS, the MS specialists reached a clear consensus (more than 75%)—MRI lesions are considered predictive of disease activity and a follow-up MRI within three to six months is important to confirm treatment effect. Optic neuritis alone was viewed as insufficient for initiating therapy. Glatiramer acetate and interferon beta were the most common initial therapy choices for CIS.

When treating RRMS with mild symptoms, most respondents also chose interferon beta and glatiramer acetate as their preferred initial therapy choices. “Treatment-naive patients with RRMS are generally started on a disease-modifying therapy,” the researchers concluded. “Disease-modifying therapies are generally switched with three or more new lesions on brain MRI over 12 months.”

The survey respondents also reached a consensus that MRI change over 12 months is a criterion for switching therapies in patients with RRMS and breakthrough disease, despite treatment with a first-line disease-modifying therapy. When interferon beta was used to treat these patients, there was a general trend toward using natalizumab as the disease progressed. For RIS, survey respondents agreed that “a spinal cord MRI is generally performed as part of the diagnostic evaluation,” and that lumbar puncture does not seem to have a major diagnostic role.

“For RRMS, the data suggested that with growing clinical experience and an increasing variety of therapeutic options, physicians may feel more confident in the use of more complex agents and treatment regimens,” the investigators stated. “The finding that nearly all respondents would perform a follow-up MRI for RIS reflects physician recognition that some patients with RIS will develop clinically definite MS and suggests that this cohort should be monitored for MRI lesion progression or evidence of clinical MS disease activity."

Two surveys of American multiple sclerosis (MS) specialists reveal a general consensus of practice patterns in primary and secondary progressive MS, relapsing-remitting MS, and clinically isolated syndrome.

AMSTERDAM—Neurologists from multiple sclerosis (MS) treatment centers across the US generally agree on the use of spinal MRI or lumbar puncture for diagnosis of the disease, but more research regarding treatment responses and therapies is needed, according to the results of two studies presented at the 5th Joint Triennial Congress of the European Committee for Treatment and Research in Multiple Sclerosis/Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).

“The current research effort was conducted with the goal of gaining an understanding of the current diagnostic and treatment practices of MS specialists at US MS treatment centers,” the investigators stated. The surveys were designed to determine the influence and use of various diagnostic and clinical parameters in clinical decisions pertaining to disease-modifying therapy initiation, switching, and selection.

The team of researchers, led by Omar A. Khan, MD, from the Department of Neurology at Wayne State University in Detroit, and Carlo Tornatore, MD, from the Department of Neurology at Georgetown University in Washington, DC, invited neurologists from 207 MS treatment centers to participate in the study. Two web-based surveys evaluating practice patterns for various forms of MS were developed and distributed to specialists; 75 specialists completed the first survey, and 71 of those completed the second survey.

CIS, RIS, and RRMS
The investigators presented participating MS specialists with patient scenarios regarding clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and radiologically isolated syndrome (RIS). Regarding CIS, the MS specialists reached a clear consensus (more than 75%)—MRI lesions are considered predictive of disease activity and a follow-up MRI within three to six months is important to confirm treatment effect. Optic neuritis alone was viewed as insufficient for initiating therapy. Glatiramer acetate and interferon beta were the most common initial therapy choices for CIS.

When treating RRMS with mild symptoms, most respondents also chose interferon beta and glatiramer acetate as their preferred initial therapy choices. “Treatment-naive patients with RRMS are generally started on a disease-modifying therapy,” the researchers concluded. “Disease-modifying therapies are generally switched with three or more new lesions on brain MRI over 12 months.”

The survey respondents also reached a consensus that MRI change over 12 months is a criterion for switching therapies in patients with RRMS and breakthrough disease, despite treatment with a first-line disease-modifying therapy. When interferon beta was used to treat these patients, there was a general trend toward using natalizumab as the disease progressed. For RIS, survey respondents agreed that “a spinal cord MRI is generally performed as part of the diagnostic evaluation,” and that lumbar puncture does not seem to have a major diagnostic role.

“For RRMS, the data suggested that with growing clinical experience and an increasing variety of therapeutic options, physicians may feel more confident in the use of more complex agents and treatment regimens,” the investigators stated. “The finding that nearly all respondents would perform a follow-up MRI for RIS reflects physician recognition that some patients with RIS will develop clinically definite MS and suggests that this cohort should be monitored for MRI lesion progression or evidence of clinical MS disease activity."

Two surveys of American multiple sclerosis (MS) specialists reveal a general consensus of practice patterns in primary and secondary progressive MS, relapsing-remitting MS, and clinically isolated syndrome.

AMSTERDAM—Neurologists from multiple sclerosis (MS) treatment centers across the US generally agree on the use of spinal MRI or lumbar puncture for diagnosis of the disease, but more research regarding treatment responses and therapies is needed, according to the results of two studies presented at the 5th Joint Triennial Congress of the European Committee for Treatment and Research in Multiple Sclerosis/Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).

“The current research effort was conducted with the goal of gaining an understanding of the current diagnostic and treatment practices of MS specialists at US MS treatment centers,” the investigators stated. The surveys were designed to determine the influence and use of various diagnostic and clinical parameters in clinical decisions pertaining to disease-modifying therapy initiation, switching, and selection.

The team of researchers, led by Omar A. Khan, MD, from the Department of Neurology at Wayne State University in Detroit, and Carlo Tornatore, MD, from the Department of Neurology at Georgetown University in Washington, DC, invited neurologists from 207 MS treatment centers to participate in the study. Two web-based surveys evaluating practice patterns for various forms of MS were developed and distributed to specialists; 75 specialists completed the first survey, and 71 of those completed the second survey.

CIS, RIS, and RRMS
The investigators presented participating MS specialists with patient scenarios regarding clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and radiologically isolated syndrome (RIS). Regarding CIS, the MS specialists reached a clear consensus (more than 75%)—MRI lesions are considered predictive of disease activity and a follow-up MRI within three to six months is important to confirm treatment effect. Optic neuritis alone was viewed as insufficient for initiating therapy. Glatiramer acetate and interferon beta were the most common initial therapy choices for CIS.

When treating RRMS with mild symptoms, most respondents also chose interferon beta and glatiramer acetate as their preferred initial therapy choices. “Treatment-naive patients with RRMS are generally started on a disease-modifying therapy,” the researchers concluded. “Disease-modifying therapies are generally switched with three or more new lesions on brain MRI over 12 months.”

The survey respondents also reached a consensus that MRI change over 12 months is a criterion for switching therapies in patients with RRMS and breakthrough disease, despite treatment with a first-line disease-modifying therapy. When interferon beta was used to treat these patients, there was a general trend toward using natalizumab as the disease progressed. For RIS, survey respondents agreed that “a spinal cord MRI is generally performed as part of the diagnostic evaluation,” and that lumbar puncture does not seem to have a major diagnostic role.

“For RRMS, the data suggested that with growing clinical experience and an increasing variety of therapeutic options, physicians may feel more confident in the use of more complex agents and treatment regimens,” the investigators stated. “The finding that nearly all respondents would perform a follow-up MRI for RIS reflects physician recognition that some patients with RIS will develop clinically definite MS and suggests that this cohort should be monitored for MRI lesion progression or evidence of clinical MS disease activity."