Multiple Sclerosis

Key clinical point: Providers should consider screening for hazardous cannabis use, especially if patients report depression, anxiety, or difficulty sleeping.

Major finding: Patients with MS who are depressed, anxious, or have poor sleep may be more likely to misuse or abuse cannabis.

Study details: 100 patients with a confirmed MS diagnosis who were receiving outpatient care in a university-affiliated MS center.

Disclosures: No study funding was reported and the authors report no relevant disclosures.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Providers should consider screening for hazardous cannabis use, especially if patients report depression, anxiety, or difficulty sleeping.

Major finding: Patients with MS who are depressed, anxious, or have poor sleep may be more likely to misuse or abuse cannabis.

Study details: 100 patients with a confirmed MS diagnosis who were receiving outpatient care in a university-affiliated MS center.

Disclosures: No study funding was reported and the authors report no relevant disclosures.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Providers should consider screening for hazardous cannabis use, especially if patients report depression, anxiety, or difficulty sleeping.

Major finding: Patients with MS who are depressed, anxious, or have poor sleep may be more likely to misuse or abuse cannabis.

Study details: 100 patients with a confirmed MS diagnosis who were receiving outpatient care in a university-affiliated MS center.

Disclosures: No study funding was reported and the authors report no relevant disclosures.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Lapses in the use of MS disease-modifying oral therapy increases the risk for relapse, hospitalization, emergency department visits, and outpatient visits, and leads to higher healthcare costs.

Major finding: Over an 18-month follow-up period, those with drug lapses of more than 60 days had 28% more relapses than did the other subjects (mean 1.2 vs. 0.8; P less than .0001).

Study details: A claims database study of 8,779 patients with MS during 2011-2015

Disclosures: EMD Serono, a division of Merck KGaA, provided funding for the study. Dr. Nicholas disclosed grant support from EMD Serono, and two other study authors are employees of the company. Another two authors worked for a consulting firm that received funding from EMD Serono to conduct the study.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Lapses in the use of MS disease-modifying oral therapy increases the risk for relapse, hospitalization, emergency department visits, and outpatient visits, and leads to higher healthcare costs.

Major finding: Over an 18-month follow-up period, those with drug lapses of more than 60 days had 28% more relapses than did the other subjects (mean 1.2 vs. 0.8; P less than .0001).

Study details: A claims database study of 8,779 patients with MS during 2011-2015

Disclosures: EMD Serono, a division of Merck KGaA, provided funding for the study. Dr. Nicholas disclosed grant support from EMD Serono, and two other study authors are employees of the company. Another two authors worked for a consulting firm that received funding from EMD Serono to conduct the study.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Lapses in the use of MS disease-modifying oral therapy increases the risk for relapse, hospitalization, emergency department visits, and outpatient visits, and leads to higher healthcare costs.

Major finding: Over an 18-month follow-up period, those with drug lapses of more than 60 days had 28% more relapses than did the other subjects (mean 1.2 vs. 0.8; P less than .0001).

Study details: A claims database study of 8,779 patients with MS during 2011-2015

Disclosures: EMD Serono, a division of Merck KGaA, provided funding for the study. Dr. Nicholas disclosed grant support from EMD Serono, and two other study authors are employees of the company. Another two authors worked for a consulting firm that received funding from EMD Serono to conduct the study.

Citation: REPORTING FROM CMSC 2019

Key clinical point: Adherence to current oral therapies for multiple sclerosis (MS) is poor.

Major finding: Almost half of patients with MS discontinue their initial oral therapy.

Study details: A retrospective administrative claims study of 8,251 patients with MS.

Disclosures: The authors received no financial support for this study. Dr. Nicholas reported receiving grant support from EMD Serono.

Citation: Nicholas J et al. CMSC 2019. Abstract DXT34.

Key clinical point: Adherence to current oral therapies for multiple sclerosis (MS) is poor.

Major finding: Almost half of patients with MS discontinue their initial oral therapy.

Study details: A retrospective administrative claims study of 8,251 patients with MS.

Disclosures: The authors received no financial support for this study. Dr. Nicholas reported receiving grant support from EMD Serono.

Citation: Nicholas J et al. CMSC 2019. Abstract DXT34.

Key clinical point: Adherence to current oral therapies for multiple sclerosis (MS) is poor.

Major finding: Almost half of patients with MS discontinue their initial oral therapy.

Study details: A retrospective administrative claims study of 8,251 patients with MS.

Disclosures: The authors received no financial support for this study. Dr. Nicholas reported receiving grant support from EMD Serono.

Citation: Nicholas J et al. CMSC 2019. Abstract DXT34.

SEATTLE – The one constant in multiple sclerosis (MS) is its lack of constancy. “As our lives are dynamic and change over time, MS is also dynamic and changes over time.” This is especially the case in women, noted Mitzi Joi Williams, MD.

bowdenimages/iStock/Getty Images

About three in four people with MS are female – about 750,000 in the United States. And the risk and incidence may be highest in African American women.

In a presentation about the unique needs of women with MS, Dr. Williams, an assistant professor of internal medicine at the Morehouse School of Medicine in Atlanta, offered these tips at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pay attention to sexual dysfunction

Patients with MS often are ashamed to talk about sexual dysfunction, Dr. Williams said, but it is on many minds. “If I have a program on intimacy in MS, people are out the door.”

She urged colleagues to understand that MS can affect sexuality through three routes: primary, secondary, and tertiary dysfunction.

In primary sexual dysfunction, brain and spinal lesions directly related to MS can cause problems such as lack of sensation or abnormal sensations, decreased libido, vaginal dryness, and difficult orgasm.

Secondary sexual dysfunction refers to problems caused by symptoms of MS such as fatigue, which can worsen as the day progresses and affect nighttime intimacy, she said. Bladder dysfunction is another sensitive area in sexuality, with patients – especially women – “concerned that they will lose control of their bladder or they have already lost control.”

Cognitive dysfunction also can disrupt sexual function. “It is important to focus, and certain things cannot happen if you do not. If you are not able to focus and concentrate, it can affect interest,” Dr. Williams said.

Additionally, medications can improve some symptoms while making others worse. For example, a drug may relieve spasticity but boost fatigue. “We have to walk this tightrope,” she said. “But if we are not asking our patients, they may not volunteer this information.”

Finally, she said, MS can spark tertiary sexual dysfunction – poor body image, depression, anxiety, and disruptive changes in familial roles. For example, one partner may become a caregiver, and “it is hard to go from caregiving to sexy time.”

“It is something we have to acknowledge and find ways to deal with,” Dr. Williams said.

To address these issues, she pointed to strategies for symptomatic relief and disease-modifying therapy (DMT) and pinpointed several treatment options.

• Fatigue – stimulants, diet, exercise.
• Spasticity – muscle relaxants, exercise.
• Bladder dysfunction – fluid restriction, medication.
• Paresthesia – antidepressants, anticonvulsants.
• Numbness – vibrators, devices to increase stimulation.

Sexual therapy, couples therapy, and pelvic floor physical therapy also can be helpful.

Be aware of special needs during prepregnancy and pregnancy

“MS itself does not have a lot of effects on fertility, pregnancy, or pregnancy outcomes,” Dr. Williams said. However, “medications cause concern about how we manage pregnancy and fertility.”

In vitro fertilization may increase the risk of relapse, she added, and patients on dimethyl fumarate who experience vomiting or diarrhea may not be able to properly absorb oral contraceptives.

Women with MS may not need to go off DMT when they are trying to conceive, she said. “If patients have very aggressive disease, they may need to be on DMT through conception, through the first trimester, and even the entire pregnancy to prevent long-term disability.”

What about pregnancy itself? “An MS diagnosis alone does not mean that a pregnancy is high risk,” she said. “There are not necessarily additional tests and ultrasounds that are recommended for our patients based on MS diagnosis alone.”

Treatment discontinuation may be warranted during pregnancy, when MS generally improves. However, some MS symptoms – fatigue, bladder dysfunction, and balance – may increase. Corticosteroids can be appropriate if relapses occur during pregnancy.

Menopause and MS symptoms may overlap

Symptoms such as hot flashes, mood changes, sleep disturbance, bladder dysfunction, and decreased energy may be signs of MS, or they could indicate menopause, Dr. Williams said. “Sometimes patients come in and they are getting worse, and we look into it and discover they are premenopausal.”

A decline in estrogen during menopause may worsen MS symptoms, she added, and hormone therapy may be appropriate. A phase 2 study found a benefit in menopausal patients with MS for estriol in conjunction with a DMT, but more studies are needed.

Dr. Williams reported no relevant financial disclosures.

SEATTLE – The one constant in multiple sclerosis (MS) is its lack of constancy. “As our lives are dynamic and change over time, MS is also dynamic and changes over time.” This is especially the case in women, noted Mitzi Joi Williams, MD.

bowdenimages/iStock/Getty Images

About three in four people with MS are female – about 750,000 in the United States. And the risk and incidence may be highest in African American women.

In a presentation about the unique needs of women with MS, Dr. Williams, an assistant professor of internal medicine at the Morehouse School of Medicine in Atlanta, offered these tips at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pay attention to sexual dysfunction

Patients with MS often are ashamed to talk about sexual dysfunction, Dr. Williams said, but it is on many minds. “If I have a program on intimacy in MS, people are out the door.”

She urged colleagues to understand that MS can affect sexuality through three routes: primary, secondary, and tertiary dysfunction.

In primary sexual dysfunction, brain and spinal lesions directly related to MS can cause problems such as lack of sensation or abnormal sensations, decreased libido, vaginal dryness, and difficult orgasm.

Secondary sexual dysfunction refers to problems caused by symptoms of MS such as fatigue, which can worsen as the day progresses and affect nighttime intimacy, she said. Bladder dysfunction is another sensitive area in sexuality, with patients – especially women – “concerned that they will lose control of their bladder or they have already lost control.”

Cognitive dysfunction also can disrupt sexual function. “It is important to focus, and certain things cannot happen if you do not. If you are not able to focus and concentrate, it can affect interest,” Dr. Williams said.

Additionally, medications can improve some symptoms while making others worse. For example, a drug may relieve spasticity but boost fatigue. “We have to walk this tightrope,” she said. “But if we are not asking our patients, they may not volunteer this information.”

Finally, she said, MS can spark tertiary sexual dysfunction – poor body image, depression, anxiety, and disruptive changes in familial roles. For example, one partner may become a caregiver, and “it is hard to go from caregiving to sexy time.”

“It is something we have to acknowledge and find ways to deal with,” Dr. Williams said.

To address these issues, she pointed to strategies for symptomatic relief and disease-modifying therapy (DMT) and pinpointed several treatment options.

• Fatigue – stimulants, diet, exercise.
• Spasticity – muscle relaxants, exercise.
• Bladder dysfunction – fluid restriction, medication.
• Paresthesia – antidepressants, anticonvulsants.
• Numbness – vibrators, devices to increase stimulation.

Sexual therapy, couples therapy, and pelvic floor physical therapy also can be helpful.

Be aware of special needs during prepregnancy and pregnancy

“MS itself does not have a lot of effects on fertility, pregnancy, or pregnancy outcomes,” Dr. Williams said. However, “medications cause concern about how we manage pregnancy and fertility.”

In vitro fertilization may increase the risk of relapse, she added, and patients on dimethyl fumarate who experience vomiting or diarrhea may not be able to properly absorb oral contraceptives.

Women with MS may not need to go off DMT when they are trying to conceive, she said. “If patients have very aggressive disease, they may need to be on DMT through conception, through the first trimester, and even the entire pregnancy to prevent long-term disability.”

What about pregnancy itself? “An MS diagnosis alone does not mean that a pregnancy is high risk,” she said. “There are not necessarily additional tests and ultrasounds that are recommended for our patients based on MS diagnosis alone.”

Treatment discontinuation may be warranted during pregnancy, when MS generally improves. However, some MS symptoms – fatigue, bladder dysfunction, and balance – may increase. Corticosteroids can be appropriate if relapses occur during pregnancy.

Menopause and MS symptoms may overlap

Symptoms such as hot flashes, mood changes, sleep disturbance, bladder dysfunction, and decreased energy may be signs of MS, or they could indicate menopause, Dr. Williams said. “Sometimes patients come in and they are getting worse, and we look into it and discover they are premenopausal.”

A decline in estrogen during menopause may worsen MS symptoms, she added, and hormone therapy may be appropriate. A phase 2 study found a benefit in menopausal patients with MS for estriol in conjunction with a DMT, but more studies are needed.

Dr. Williams reported no relevant financial disclosures.

SEATTLE – The one constant in multiple sclerosis (MS) is its lack of constancy. “As our lives are dynamic and change over time, MS is also dynamic and changes over time.” This is especially the case in women, noted Mitzi Joi Williams, MD.

bowdenimages/iStock/Getty Images

About three in four people with MS are female – about 750,000 in the United States. And the risk and incidence may be highest in African American women.

In a presentation about the unique needs of women with MS, Dr. Williams, an assistant professor of internal medicine at the Morehouse School of Medicine in Atlanta, offered these tips at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pay attention to sexual dysfunction

Patients with MS often are ashamed to talk about sexual dysfunction, Dr. Williams said, but it is on many minds. “If I have a program on intimacy in MS, people are out the door.”

She urged colleagues to understand that MS can affect sexuality through three routes: primary, secondary, and tertiary dysfunction.

In primary sexual dysfunction, brain and spinal lesions directly related to MS can cause problems such as lack of sensation or abnormal sensations, decreased libido, vaginal dryness, and difficult orgasm.

Secondary sexual dysfunction refers to problems caused by symptoms of MS such as fatigue, which can worsen as the day progresses and affect nighttime intimacy, she said. Bladder dysfunction is another sensitive area in sexuality, with patients – especially women – “concerned that they will lose control of their bladder or they have already lost control.”

Cognitive dysfunction also can disrupt sexual function. “It is important to focus, and certain things cannot happen if you do not. If you are not able to focus and concentrate, it can affect interest,” Dr. Williams said.

Additionally, medications can improve some symptoms while making others worse. For example, a drug may relieve spasticity but boost fatigue. “We have to walk this tightrope,” she said. “But if we are not asking our patients, they may not volunteer this information.”

Finally, she said, MS can spark tertiary sexual dysfunction – poor body image, depression, anxiety, and disruptive changes in familial roles. For example, one partner may become a caregiver, and “it is hard to go from caregiving to sexy time.”

“It is something we have to acknowledge and find ways to deal with,” Dr. Williams said.

To address these issues, she pointed to strategies for symptomatic relief and disease-modifying therapy (DMT) and pinpointed several treatment options.

• Fatigue – stimulants, diet, exercise.
• Spasticity – muscle relaxants, exercise.
• Bladder dysfunction – fluid restriction, medication.
• Paresthesia – antidepressants, anticonvulsants.
• Numbness – vibrators, devices to increase stimulation.

Sexual therapy, couples therapy, and pelvic floor physical therapy also can be helpful.

Be aware of special needs during prepregnancy and pregnancy

“MS itself does not have a lot of effects on fertility, pregnancy, or pregnancy outcomes,” Dr. Williams said. However, “medications cause concern about how we manage pregnancy and fertility.”

In vitro fertilization may increase the risk of relapse, she added, and patients on dimethyl fumarate who experience vomiting or diarrhea may not be able to properly absorb oral contraceptives.

Women with MS may not need to go off DMT when they are trying to conceive, she said. “If patients have very aggressive disease, they may need to be on DMT through conception, through the first trimester, and even the entire pregnancy to prevent long-term disability.”

What about pregnancy itself? “An MS diagnosis alone does not mean that a pregnancy is high risk,” she said. “There are not necessarily additional tests and ultrasounds that are recommended for our patients based on MS diagnosis alone.”

Treatment discontinuation may be warranted during pregnancy, when MS generally improves. However, some MS symptoms – fatigue, bladder dysfunction, and balance – may increase. Corticosteroids can be appropriate if relapses occur during pregnancy.

Menopause and MS symptoms may overlap

Symptoms such as hot flashes, mood changes, sleep disturbance, bladder dysfunction, and decreased energy may be signs of MS, or they could indicate menopause, Dr. Williams said. “Sometimes patients come in and they are getting worse, and we look into it and discover they are premenopausal.”

A decline in estrogen during menopause may worsen MS symptoms, she added, and hormone therapy may be appropriate. A phase 2 study found a benefit in menopausal patients with MS for estriol in conjunction with a DMT, but more studies are needed.

Dr. Williams reported no relevant financial disclosures.

SEATTLE – Multiple sclerosis (MS) presents quite differently in children than adults, a neurologist told colleagues, but many treatments are the same. The key is to remember the unique needs of pediatric MS patients, their specific challenges, and the difference that can be made through therapy.

Brian Hoyle/MDedge News

“We need to treat them when they’re young, perhaps, to prevent disability later on,” said Jennifer Graves, MD, PhD, director of neuroimmunology research at the University of California, San Diego, and director of the Rady Children’s Pediatric MS Clinic.

Fortunately, “they tend to respond to any DMT [disease-modifying therapy] you give them,” said Dr. Graves, who spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Unlike the adult version, pediatric MS is almost never progressive, she said, and the relapsing form affects 85%-99% of those with the condition.

And children with MS suffer from high relapse rates. “In some of the more recent studies, the annual relapse rates have been two to even five to six times higher than in adults,” she related.

For acute relapses, Dr. Graves recommends IV methylprednisolone as a first-line treatment. High-dose oral steroids can be appropriate in teenagers, and plasma exchange is a second-line option.

DMT does work in children. “They’re just so inflammatory, having so much activity, that they tend to respond to anything,” she noted.

With few exceptions, DMTs have been tested in children, she said. But the trials in children have tended to be small, and only fingolimod (Gilenya) is Food and Drug Administration–approved for pediatric patients (aged 10-18 years).

What’s the best DMT for kids? “There is evidence that the higher-potency drugs may work better in some patients,” Dr. Graves said. “I diagnosed a 4 year old with MS. With an annual relapse rate of 6, I had no hesitancy about jumping to the highest-potency agent I had available.”

She cautioned, however, that there may never be deep insight into the best choices because of it is not feasible to study all the available DMTs in children.

Dr. Graves offered these tips about treating children with MS:

• Be prepared to spend long periods educating children and their parents. “You think you spend a long time with your adult patients? Double it,” she said. “Most new patient appointments will be 90 minutes at least. Negotiate that time for the patients in your clinic who are very young.”
• Don’t separate kids from parents. “I discourage parents from asking their children to leave the room. Everyone should know what the choices are as much as possible and having the children on the same page can help with compliance,” Dr. Graves said.
• Consider unique safety considerations. “Children are less likely to be JC [John Cunningham] virus antibody-positive than adults, and we can feel more confident with agents that cause PML [progressive multifocal leukoencephalopathy],” she said. “But they’re more likely to convert on our watch.”
• Consider mentioning sexual function to teens. As adolescents, “they’re unsure of sexual function to begin with, and they often don’t know if they’re normal in terms of sexual function.” Don’t forget that contraceptives may be appropriate because some MS drugs are teratogenic. “Have a lengthy and realistic conversation about birth control,” Dr. Graves said, “and maybe ask the parents to leave the room.”

Dr. Graves disclosed receiving speaking honoraria from Novartis and Sanofi Genzyme, and grants from Biogen and Genentech.

SEATTLE – Multiple sclerosis (MS) presents quite differently in children than adults, a neurologist told colleagues, but many treatments are the same. The key is to remember the unique needs of pediatric MS patients, their specific challenges, and the difference that can be made through therapy.

Brian Hoyle/MDedge News

“We need to treat them when they’re young, perhaps, to prevent disability later on,” said Jennifer Graves, MD, PhD, director of neuroimmunology research at the University of California, San Diego, and director of the Rady Children’s Pediatric MS Clinic.

Fortunately, “they tend to respond to any DMT [disease-modifying therapy] you give them,” said Dr. Graves, who spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Unlike the adult version, pediatric MS is almost never progressive, she said, and the relapsing form affects 85%-99% of those with the condition.

And children with MS suffer from high relapse rates. “In some of the more recent studies, the annual relapse rates have been two to even five to six times higher than in adults,” she related.

For acute relapses, Dr. Graves recommends IV methylprednisolone as a first-line treatment. High-dose oral steroids can be appropriate in teenagers, and plasma exchange is a second-line option.

DMT does work in children. “They’re just so inflammatory, having so much activity, that they tend to respond to anything,” she noted.

With few exceptions, DMTs have been tested in children, she said. But the trials in children have tended to be small, and only fingolimod (Gilenya) is Food and Drug Administration–approved for pediatric patients (aged 10-18 years).

What’s the best DMT for kids? “There is evidence that the higher-potency drugs may work better in some patients,” Dr. Graves said. “I diagnosed a 4 year old with MS. With an annual relapse rate of 6, I had no hesitancy about jumping to the highest-potency agent I had available.”

She cautioned, however, that there may never be deep insight into the best choices because of it is not feasible to study all the available DMTs in children.

Dr. Graves offered these tips about treating children with MS:

• Be prepared to spend long periods educating children and their parents. “You think you spend a long time with your adult patients? Double it,” she said. “Most new patient appointments will be 90 minutes at least. Negotiate that time for the patients in your clinic who are very young.”
• Don’t separate kids from parents. “I discourage parents from asking their children to leave the room. Everyone should know what the choices are as much as possible and having the children on the same page can help with compliance,” Dr. Graves said.
• Consider unique safety considerations. “Children are less likely to be JC [John Cunningham] virus antibody-positive than adults, and we can feel more confident with agents that cause PML [progressive multifocal leukoencephalopathy],” she said. “But they’re more likely to convert on our watch.”
• Consider mentioning sexual function to teens. As adolescents, “they’re unsure of sexual function to begin with, and they often don’t know if they’re normal in terms of sexual function.” Don’t forget that contraceptives may be appropriate because some MS drugs are teratogenic. “Have a lengthy and realistic conversation about birth control,” Dr. Graves said, “and maybe ask the parents to leave the room.”

Dr. Graves disclosed receiving speaking honoraria from Novartis and Sanofi Genzyme, and grants from Biogen and Genentech.

SEATTLE – Multiple sclerosis (MS) presents quite differently in children than adults, a neurologist told colleagues, but many treatments are the same. The key is to remember the unique needs of pediatric MS patients, their specific challenges, and the difference that can be made through therapy.

Brian Hoyle/MDedge News

“We need to treat them when they’re young, perhaps, to prevent disability later on,” said Jennifer Graves, MD, PhD, director of neuroimmunology research at the University of California, San Diego, and director of the Rady Children’s Pediatric MS Clinic.

Fortunately, “they tend to respond to any DMT [disease-modifying therapy] you give them,” said Dr. Graves, who spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Unlike the adult version, pediatric MS is almost never progressive, she said, and the relapsing form affects 85%-99% of those with the condition.

And children with MS suffer from high relapse rates. “In some of the more recent studies, the annual relapse rates have been two to even five to six times higher than in adults,” she related.

For acute relapses, Dr. Graves recommends IV methylprednisolone as a first-line treatment. High-dose oral steroids can be appropriate in teenagers, and plasma exchange is a second-line option.

DMT does work in children. “They’re just so inflammatory, having so much activity, that they tend to respond to anything,” she noted.

With few exceptions, DMTs have been tested in children, she said. But the trials in children have tended to be small, and only fingolimod (Gilenya) is Food and Drug Administration–approved for pediatric patients (aged 10-18 years).

What’s the best DMT for kids? “There is evidence that the higher-potency drugs may work better in some patients,” Dr. Graves said. “I diagnosed a 4 year old with MS. With an annual relapse rate of 6, I had no hesitancy about jumping to the highest-potency agent I had available.”

She cautioned, however, that there may never be deep insight into the best choices because of it is not feasible to study all the available DMTs in children.

Dr. Graves offered these tips about treating children with MS:

• Be prepared to spend long periods educating children and their parents. “You think you spend a long time with your adult patients? Double it,” she said. “Most new patient appointments will be 90 minutes at least. Negotiate that time for the patients in your clinic who are very young.”
• Don’t separate kids from parents. “I discourage parents from asking their children to leave the room. Everyone should know what the choices are as much as possible and having the children on the same page can help with compliance,” Dr. Graves said.
• Consider unique safety considerations. “Children are less likely to be JC [John Cunningham] virus antibody-positive than adults, and we can feel more confident with agents that cause PML [progressive multifocal leukoencephalopathy],” she said. “But they’re more likely to convert on our watch.”
• Consider mentioning sexual function to teens. As adolescents, “they’re unsure of sexual function to begin with, and they often don’t know if they’re normal in terms of sexual function.” Don’t forget that contraceptives may be appropriate because some MS drugs are teratogenic. “Have a lengthy and realistic conversation about birth control,” Dr. Graves said, “and maybe ask the parents to leave the room.”

Dr. Graves disclosed receiving speaking honoraria from Novartis and Sanofi Genzyme, and grants from Biogen and Genentech.

SEATTLE – Finding a balance between maintaining patient privacy and preventing self-harm is crucial in multiple sclerosis patients at risk for suicide.

“There are some situations where concern for a patient’s safety overrides [confidentiality],” Lauren Sankary, an attorney and neuroethics fellow at the Cleveland Clinic, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “I want to empower you to feel confident to break confidentiality when it makes sense based on your professional judgment.”

It’s not clear whether suicide is more common in patients with MS. A systematic review from 2012 found that most studies reviewed documented a higher rate of suicide in patients with MS, compared with the general population (J Psychosom Res. 2012 Dec;73(6):411-7) while a report from 2017 noted that rates of suicidal intent were elevated in MS (Mult Scler. 2017 Jun;23(7):923-927). Conversely, a French study from 2017 found that excess suicide risk may not be true for MS patients (Mult Scler. 2017 May;23(6):864-871).

When considering breaking confidentiality to seek help for a patient, Ms. Sankary said, “the ethical tension is that on the one hand, disclosing protected health information may protect patient safety. But on the other hand, it may threaten the therapeutic relationship. It’s a true ethical dilemma, and part of what’s difficult is figuring out in which situations are we willing to accept these tradeoffs.”

Consider professional ethical guidelines, federal and local laws, and clinical protocols in the decision making process, she advised.

On the federal level, HIPAA allows the breaking of confidentiality when it “is necessary to prevent or lessen a serious and imminent threat to the health or safety of a person or the public.”

The U.S. Department of Health & Human Services’ Office of Civil Rights notes that “HIPAA permits a covered health care provider to notify a patient’s family members of a serious and imminent threat to the health or safety of the patient or others if those family members are in a position to lessen or avert the threat. Thus, to the extent that a provider determines that there is a serious and imminent threat of a patient physically harming self or others, HIPAA would permit the provider to warn the appropriate person(s) of the threat, consistent with his or her professional ethical obligations and State law requirements.”

Confidential information cannot be disclosed to just anyone, however. HIPAA notes that it must be disclosed only to “a person or persons reasonably able to prevent or lessen the threat, including the target of the threat.”

HIPAA doesn’t require medical professionals to report suicide risk, Ms. Sankary said, but some states require certain professionals to do so. And some states require certain professionals to alert parents if children are suicidal.

The laws mainly affect mental health professionals but may extend to physicians and nurses, according to the National Conference of State Legislators. For example, New Jersey professionals in several fields have a duty to warn in certain situations, including the risk of self-harm.

The American Medical Association’s Code of Medical Ethics suggests physicians must “inform the patient when there has been a significant infringement on privacy of which the patient would otherwise not be aware,” Ms. Sankary said.

Ms. Sankary reported no relevant disclosures.

SEATTLE – Finding a balance between maintaining patient privacy and preventing self-harm is crucial in multiple sclerosis patients at risk for suicide.

“There are some situations where concern for a patient’s safety overrides [confidentiality],” Lauren Sankary, an attorney and neuroethics fellow at the Cleveland Clinic, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “I want to empower you to feel confident to break confidentiality when it makes sense based on your professional judgment.”

It’s not clear whether suicide is more common in patients with MS. A systematic review from 2012 found that most studies reviewed documented a higher rate of suicide in patients with MS, compared with the general population (J Psychosom Res. 2012 Dec;73(6):411-7) while a report from 2017 noted that rates of suicidal intent were elevated in MS (Mult Scler. 2017 Jun;23(7):923-927). Conversely, a French study from 2017 found that excess suicide risk may not be true for MS patients (Mult Scler. 2017 May;23(6):864-871).

When considering breaking confidentiality to seek help for a patient, Ms. Sankary said, “the ethical tension is that on the one hand, disclosing protected health information may protect patient safety. But on the other hand, it may threaten the therapeutic relationship. It’s a true ethical dilemma, and part of what’s difficult is figuring out in which situations are we willing to accept these tradeoffs.”

Consider professional ethical guidelines, federal and local laws, and clinical protocols in the decision making process, she advised.

On the federal level, HIPAA allows the breaking of confidentiality when it “is necessary to prevent or lessen a serious and imminent threat to the health or safety of a person or the public.”

The U.S. Department of Health & Human Services’ Office of Civil Rights notes that “HIPAA permits a covered health care provider to notify a patient’s family members of a serious and imminent threat to the health or safety of the patient or others if those family members are in a position to lessen or avert the threat. Thus, to the extent that a provider determines that there is a serious and imminent threat of a patient physically harming self or others, HIPAA would permit the provider to warn the appropriate person(s) of the threat, consistent with his or her professional ethical obligations and State law requirements.”

Confidential information cannot be disclosed to just anyone, however. HIPAA notes that it must be disclosed only to “a person or persons reasonably able to prevent or lessen the threat, including the target of the threat.”

HIPAA doesn’t require medical professionals to report suicide risk, Ms. Sankary said, but some states require certain professionals to do so. And some states require certain professionals to alert parents if children are suicidal.

The laws mainly affect mental health professionals but may extend to physicians and nurses, according to the National Conference of State Legislators. For example, New Jersey professionals in several fields have a duty to warn in certain situations, including the risk of self-harm.

The American Medical Association’s Code of Medical Ethics suggests physicians must “inform the patient when there has been a significant infringement on privacy of which the patient would otherwise not be aware,” Ms. Sankary said.

Ms. Sankary reported no relevant disclosures.

SEATTLE – Finding a balance between maintaining patient privacy and preventing self-harm is crucial in multiple sclerosis patients at risk for suicide.

“There are some situations where concern for a patient’s safety overrides [confidentiality],” Lauren Sankary, an attorney and neuroethics fellow at the Cleveland Clinic, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “I want to empower you to feel confident to break confidentiality when it makes sense based on your professional judgment.”

It’s not clear whether suicide is more common in patients with MS. A systematic review from 2012 found that most studies reviewed documented a higher rate of suicide in patients with MS, compared with the general population (J Psychosom Res. 2012 Dec;73(6):411-7) while a report from 2017 noted that rates of suicidal intent were elevated in MS (Mult Scler. 2017 Jun;23(7):923-927). Conversely, a French study from 2017 found that excess suicide risk may not be true for MS patients (Mult Scler. 2017 May;23(6):864-871).

When considering breaking confidentiality to seek help for a patient, Ms. Sankary said, “the ethical tension is that on the one hand, disclosing protected health information may protect patient safety. But on the other hand, it may threaten the therapeutic relationship. It’s a true ethical dilemma, and part of what’s difficult is figuring out in which situations are we willing to accept these tradeoffs.”

Consider professional ethical guidelines, federal and local laws, and clinical protocols in the decision making process, she advised.

On the federal level, HIPAA allows the breaking of confidentiality when it “is necessary to prevent or lessen a serious and imminent threat to the health or safety of a person or the public.”

The U.S. Department of Health & Human Services’ Office of Civil Rights notes that “HIPAA permits a covered health care provider to notify a patient’s family members of a serious and imminent threat to the health or safety of the patient or others if those family members are in a position to lessen or avert the threat. Thus, to the extent that a provider determines that there is a serious and imminent threat of a patient physically harming self or others, HIPAA would permit the provider to warn the appropriate person(s) of the threat, consistent with his or her professional ethical obligations and State law requirements.”

Confidential information cannot be disclosed to just anyone, however. HIPAA notes that it must be disclosed only to “a person or persons reasonably able to prevent or lessen the threat, including the target of the threat.”

HIPAA doesn’t require medical professionals to report suicide risk, Ms. Sankary said, but some states require certain professionals to do so. And some states require certain professionals to alert parents if children are suicidal.

The laws mainly affect mental health professionals but may extend to physicians and nurses, according to the National Conference of State Legislators. For example, New Jersey professionals in several fields have a duty to warn in certain situations, including the risk of self-harm.

The American Medical Association’s Code of Medical Ethics suggests physicians must “inform the patient when there has been a significant infringement on privacy of which the patient would otherwise not be aware,” Ms. Sankary said.

Ms. Sankary reported no relevant disclosures.

SEATTLE – About 65% of patients with pediatric multiple sclerosis (MS) do not receive disease-modifying therapy (DMT) within 1 year of diagnosis, according to an analysis of insurance claims data. Females may be more likely than males to receive DMT during this time, said Chinmay Deshpande, PhD, at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pediatric onset of MS occurs in 3-5% of patients with the disease, and the median age of pediatric onset is 15 years. This population tends to have a high relapse rate and may develop disability at a younger age, said Dr. Deshpande, associate director of health economics and outcomes research at Novartis. “There have been very few studies done on this population, especially in the clinical trial setting. ... Physicians face considerable uncertainty in how to treat these patients.”
 

Observational data

To assess the proportion of patients with pediatric MS who receive DMT in the year after diagnosis, Dr. Deshpande and colleagues analyzed retrospective observational data from the Truven Health Marketscan Commercial and Encounters administrative claims databases. They studied patients who received an MS diagnosis between Jan. 1, 2010, and Dec. 31, 2016. In addition, they examined which DMTs were used as first-line therapies, whether prescribing patterns changed between 2010 and 2017, and time to treatment discontinuation or switch.

The databases included data from more than 182,000 patients with two or more claims of MS diagnosis. After including only patients age 17 years or younger at the index diagnosis date who had insurance during the 6 months prior to the index date and 12 months after the index date and who did not use DMT during the 6 months prior to the index date, 288 patients remained in the analysis. Patients had an average age of about 14 years.

The primary outcome was the proportion of patients who started DMT in the year after MS diagnosis. “The proportion of untreated patients within their first year of diagnosis was around 65%,” said Dr. Deshpande. On average, treated patients were slightly older than untreated patients (15.0 years vs. 13.3 years). Among treated patients, 75% were female, and 25% were male. Overall, however, 61% were female and 39% were male. The difference in treatment by gender was surprising and the reason for it is not understood, Dr. Deshpande said. One possibility is that the difference relates to earlier maturation in females, but that is only a hypothesis, he said.

Glatiramer acetate and interferon beta-1a were first-line DMTs for 48% and 30.6% of the treated patients, respectively. Dimethyl fumarate (7.1%), natalizumab (5.1%), fingolimod (4.1%), interferon beta-1b (4.1%), and peginterferon beta-1a (1%) also were used as first-line therapy.

Twenty percent of patients who received DMT switched to another medication during the follow-up period. The median time of switching was within 6 months of starting first-line therapy. Most patients who discontinued DMT – that is, they did not have any DMT for 60 days after stopping their first DMT – did so within 10 months of diagnosis.
 

Use of newer medications

Overall, the use of glatiramer acetate and interferons has decreased over time, and while the use of newer DMTs has increased, the trend is not consistent. “With the growing uptake of newer oral and infusible DMTs over the recent years, there is a need to increase treatment awareness in the pediatric MS population and to inform currently approved treatment options to the prescribers,” Dr. Deshpande and colleagues said.

The claims database is generalizable and nationally representative, but it does not include clinical or MRI data. “It’s hard to understand the reasoning why they discontinued or why they are switching,” Dr. Deshpande said. In addition, the sample size was relatively small, and the results should be interpreted accordingly, he said.

Novartis funded the study, and Dr. Deshpande and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

[email protected]

SOURCE: Greenberg B et al. CMSC 2019, Abstract DXM02.


 

SEATTLE – About 65% of patients with pediatric multiple sclerosis (MS) do not receive disease-modifying therapy (DMT) within 1 year of diagnosis, according to an analysis of insurance claims data. Females may be more likely than males to receive DMT during this time, said Chinmay Deshpande, PhD, at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pediatric onset of MS occurs in 3-5% of patients with the disease, and the median age of pediatric onset is 15 years. This population tends to have a high relapse rate and may develop disability at a younger age, said Dr. Deshpande, associate director of health economics and outcomes research at Novartis. “There have been very few studies done on this population, especially in the clinical trial setting. ... Physicians face considerable uncertainty in how to treat these patients.”
 

Observational data

To assess the proportion of patients with pediatric MS who receive DMT in the year after diagnosis, Dr. Deshpande and colleagues analyzed retrospective observational data from the Truven Health Marketscan Commercial and Encounters administrative claims databases. They studied patients who received an MS diagnosis between Jan. 1, 2010, and Dec. 31, 2016. In addition, they examined which DMTs were used as first-line therapies, whether prescribing patterns changed between 2010 and 2017, and time to treatment discontinuation or switch.

The databases included data from more than 182,000 patients with two or more claims of MS diagnosis. After including only patients age 17 years or younger at the index diagnosis date who had insurance during the 6 months prior to the index date and 12 months after the index date and who did not use DMT during the 6 months prior to the index date, 288 patients remained in the analysis. Patients had an average age of about 14 years.

The primary outcome was the proportion of patients who started DMT in the year after MS diagnosis. “The proportion of untreated patients within their first year of diagnosis was around 65%,” said Dr. Deshpande. On average, treated patients were slightly older than untreated patients (15.0 years vs. 13.3 years). Among treated patients, 75% were female, and 25% were male. Overall, however, 61% were female and 39% were male. The difference in treatment by gender was surprising and the reason for it is not understood, Dr. Deshpande said. One possibility is that the difference relates to earlier maturation in females, but that is only a hypothesis, he said.

Glatiramer acetate and interferon beta-1a were first-line DMTs for 48% and 30.6% of the treated patients, respectively. Dimethyl fumarate (7.1%), natalizumab (5.1%), fingolimod (4.1%), interferon beta-1b (4.1%), and peginterferon beta-1a (1%) also were used as first-line therapy.

Twenty percent of patients who received DMT switched to another medication during the follow-up period. The median time of switching was within 6 months of starting first-line therapy. Most patients who discontinued DMT – that is, they did not have any DMT for 60 days after stopping their first DMT – did so within 10 months of diagnosis.
 

Use of newer medications

Overall, the use of glatiramer acetate and interferons has decreased over time, and while the use of newer DMTs has increased, the trend is not consistent. “With the growing uptake of newer oral and infusible DMTs over the recent years, there is a need to increase treatment awareness in the pediatric MS population and to inform currently approved treatment options to the prescribers,” Dr. Deshpande and colleagues said.

The claims database is generalizable and nationally representative, but it does not include clinical or MRI data. “It’s hard to understand the reasoning why they discontinued or why they are switching,” Dr. Deshpande said. In addition, the sample size was relatively small, and the results should be interpreted accordingly, he said.

Novartis funded the study, and Dr. Deshpande and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

[email protected]

SOURCE: Greenberg B et al. CMSC 2019, Abstract DXM02.


 

SEATTLE – About 65% of patients with pediatric multiple sclerosis (MS) do not receive disease-modifying therapy (DMT) within 1 year of diagnosis, according to an analysis of insurance claims data. Females may be more likely than males to receive DMT during this time, said Chinmay Deshpande, PhD, at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pediatric onset of MS occurs in 3-5% of patients with the disease, and the median age of pediatric onset is 15 years. This population tends to have a high relapse rate and may develop disability at a younger age, said Dr. Deshpande, associate director of health economics and outcomes research at Novartis. “There have been very few studies done on this population, especially in the clinical trial setting. ... Physicians face considerable uncertainty in how to treat these patients.”
 

Observational data

To assess the proportion of patients with pediatric MS who receive DMT in the year after diagnosis, Dr. Deshpande and colleagues analyzed retrospective observational data from the Truven Health Marketscan Commercial and Encounters administrative claims databases. They studied patients who received an MS diagnosis between Jan. 1, 2010, and Dec. 31, 2016. In addition, they examined which DMTs were used as first-line therapies, whether prescribing patterns changed between 2010 and 2017, and time to treatment discontinuation or switch.

The databases included data from more than 182,000 patients with two or more claims of MS diagnosis. After including only patients age 17 years or younger at the index diagnosis date who had insurance during the 6 months prior to the index date and 12 months after the index date and who did not use DMT during the 6 months prior to the index date, 288 patients remained in the analysis. Patients had an average age of about 14 years.

The primary outcome was the proportion of patients who started DMT in the year after MS diagnosis. “The proportion of untreated patients within their first year of diagnosis was around 65%,” said Dr. Deshpande. On average, treated patients were slightly older than untreated patients (15.0 years vs. 13.3 years). Among treated patients, 75% were female, and 25% were male. Overall, however, 61% were female and 39% were male. The difference in treatment by gender was surprising and the reason for it is not understood, Dr. Deshpande said. One possibility is that the difference relates to earlier maturation in females, but that is only a hypothesis, he said.

Glatiramer acetate and interferon beta-1a were first-line DMTs for 48% and 30.6% of the treated patients, respectively. Dimethyl fumarate (7.1%), natalizumab (5.1%), fingolimod (4.1%), interferon beta-1b (4.1%), and peginterferon beta-1a (1%) also were used as first-line therapy.

Twenty percent of patients who received DMT switched to another medication during the follow-up period. The median time of switching was within 6 months of starting first-line therapy. Most patients who discontinued DMT – that is, they did not have any DMT for 60 days after stopping their first DMT – did so within 10 months of diagnosis.
 

Use of newer medications

Overall, the use of glatiramer acetate and interferons has decreased over time, and while the use of newer DMTs has increased, the trend is not consistent. “With the growing uptake of newer oral and infusible DMTs over the recent years, there is a need to increase treatment awareness in the pediatric MS population and to inform currently approved treatment options to the prescribers,” Dr. Deshpande and colleagues said.

The claims database is generalizable and nationally representative, but it does not include clinical or MRI data. “It’s hard to understand the reasoning why they discontinued or why they are switching,” Dr. Deshpande said. In addition, the sample size was relatively small, and the results should be interpreted accordingly, he said.

Novartis funded the study, and Dr. Deshpande and a coauthor are employees of Novartis. Other coauthors reported consulting fees from Novartis, as well as consulting fees and grant funding from other pharmaceutical companies.

[email protected]

SOURCE: Greenberg B et al. CMSC 2019, Abstract DXM02.


 

Brenda L. Banwell, MD, is Chief of the Division of Neurology at Children’s Hospital of Philadelphia and holder of the Grace R. Loeb Endowed Chair in Neurosciences. Dr. Banwell is an expert in pediatric-onset multiple sclerosis (MS) with a clinical focus on cognitive features, neuroimaging, T and B-cell autoimmunity studies, and studies of viral triggers. We spoke with Dr. Banwell to discuss the disease course of pediatric-onset MS and the impact of magnetic resonance imaging (MRI).

How does the disease course of pediatric-onset MS differ from that of adult-onset MS?

DR. BANWELL:  Pediatric-onset MS is almost universally a relapsing-remitting disease at onset. Primary progressive MS is typically not seen in children younger than 18 years of age.

Children with progressive disability from onset should be considered more likely to have either a mitochondrial disease, genetic leukodystrophy or other disorder. Multiple sclerosis would not be a consideration for a child with progressive disability at the beginning.

Secondary progressive MS does not appear to occur for most children during the first 10 years of disease. Retrospective cohort studies suggest that secondary progressive MS in patients with pediatric-onset MS likely takes, on average, at least 20 years to occur from onset.

However, we should remember that pediatric-onset MS patients are at risk for secondary progression when they are only 30 or 35 years of age, depending on when they experienced their first attack. With the availability of numerous MS therapies, we are optimistic that secondary progressive MS may now be less likely to occur, or may be delayed even further from onset.

How often are MRIs performed on children with MS?

DR. BANWELL:  The most pivotal MRI is the one that helps you confirm the diagnosis. It is ideally obtained very close to the first onset of symptoms. That MRI could include the orbits, brain, and spine, depending on the clinical symptoms.

Following the first MRI scan, most of us would image our patients approximately every 3 months in the first year. After the first year, we would typically image our patients at least every 6 months, until, if they have been stable for an extended period of time, we might move to annual imaging.

The frequency of MRI scanning is determined by clinical disease activity, treatment decisions, and the age of the child. For example, very young children may require repeated exposure to anesthetics in order to obtain an MRI. We might have to think strategically about how often to put them under that degree of anesthesia to obtain imaging. Many young children are able to lie still for MRI if the facility has the option for viewing a video during the scan.

How do those MRI results influence your treatment decisions for the pediatric patient?

DR. BANWELL:  The International Pediatric Multiple Sclerosis Study Group recently had an international consensus discussion with respect to monitoring disease activity and are working as a collective toward the concept of defining a standard interpretation of adequate disease control for given treatments. Standardized protocols for clinical evaluations and for MRI scan interpretation will be essential. Determining what constitutes “adequate treatment response”, both in terms of relapse frequency and frequency of new lesions on MRI will be important components to consider.

What have the MRI studies shown us about the brain volume in pediatric patients with MS?

DR. BANWELL:  There are several things that we have learned about the impact of MS in the brains of children and teenagers.

With respect to brain growth and brain volume, we have learned that at the time of a first attack, children and teenagers with MS already have brain volumes that are about one standard deviation below what you would expect for someone their age and sex.

The inner skull size is also reduced, which suggests that there has been a failure of head and skull growth even before the first attack.

Following identification of MS in a child, the subsequent serial MRI studies have shown that children with MS fail to have age-expected brain growth. We do not see the age-expected rate of growth in our pediatric patients.

Around age 16 to 17 is when our brain volumes are the largest in our lifetime, but our pediatric patients show brain atrophy or progressive loss of brain volume after age 15, a time when normal brain volumes are pretty stable for at least a decade.

When we age, there is a gradual rate of brain volume loss, but this has not been imaged yet in our pediatric patients with MS since we do not have serial studies of individuals who are 30 or 40 yet who had pediatric-onset MS.

What else have MRI studies shown?

DR. BANWELL:  Another point to add is that when we look at patients with pediatric-onset MS compared with those with adult-onset MS matched for disease duration, pediatric patients on average have higher T2 and T1 lesion volumes compared with adults. This suggests that despite their young age, pediatric-onset MS patients have had sufficient time to accrue subclinical disease/lesions and may have an accelerated rate of new lesion formation.

MRI and some of the newer more advanced MRI techniques are also informing on brain tissue integrity. In studies that examine whether the white matter highways in the brain or the pathways in the brain are normal, we find that in both pediatric-onset and adult-onset MS, even normal-appearing white matter is not normal. It is not as well structured as it should be compared with age- and sex-matched controls. Further, the myelin integrity or the structural alignment in the brain of our pediatric patients may not be normal.

I think that emphasizes to all of us that MS is much more than just multiple areas of “sclerosis”  or scarring, which is what MS actually means. It is indeed a disease that has a more widespread impact on the central nervous system,  beyond the very bright T2 lesions that we normally count and measure.

That is important because it speaks to the subsequent requirement that we think about when considering treatment for MS. Our goal is to not only suppress the acquisition of new lesions, which is the common metric for clinical trials, but we also think about brain protection, brain preservation, and brain repair, which, I think, is potentially the underlying substrate that is not yet fully addressed by the evolving treatment.

Brenda L. Banwell, MD, is Chief of the Division of Neurology at Children’s Hospital of Philadelphia and holder of the Grace R. Loeb Endowed Chair in Neurosciences. Dr. Banwell is an expert in pediatric-onset multiple sclerosis (MS) with a clinical focus on cognitive features, neuroimaging, T and B-cell autoimmunity studies, and studies of viral triggers. We spoke with Dr. Banwell to discuss the disease course of pediatric-onset MS and the impact of magnetic resonance imaging (MRI).

How does the disease course of pediatric-onset MS differ from that of adult-onset MS?

DR. BANWELL:  Pediatric-onset MS is almost universally a relapsing-remitting disease at onset. Primary progressive MS is typically not seen in children younger than 18 years of age.

Children with progressive disability from onset should be considered more likely to have either a mitochondrial disease, genetic leukodystrophy or other disorder. Multiple sclerosis would not be a consideration for a child with progressive disability at the beginning.

Secondary progressive MS does not appear to occur for most children during the first 10 years of disease. Retrospective cohort studies suggest that secondary progressive MS in patients with pediatric-onset MS likely takes, on average, at least 20 years to occur from onset.

However, we should remember that pediatric-onset MS patients are at risk for secondary progression when they are only 30 or 35 years of age, depending on when they experienced their first attack. With the availability of numerous MS therapies, we are optimistic that secondary progressive MS may now be less likely to occur, or may be delayed even further from onset.

How often are MRIs performed on children with MS?

DR. BANWELL:  The most pivotal MRI is the one that helps you confirm the diagnosis. It is ideally obtained very close to the first onset of symptoms. That MRI could include the orbits, brain, and spine, depending on the clinical symptoms.

Following the first MRI scan, most of us would image our patients approximately every 3 months in the first year. After the first year, we would typically image our patients at least every 6 months, until, if they have been stable for an extended period of time, we might move to annual imaging.

The frequency of MRI scanning is determined by clinical disease activity, treatment decisions, and the age of the child. For example, very young children may require repeated exposure to anesthetics in order to obtain an MRI. We might have to think strategically about how often to put them under that degree of anesthesia to obtain imaging. Many young children are able to lie still for MRI if the facility has the option for viewing a video during the scan.

How do those MRI results influence your treatment decisions for the pediatric patient?

DR. BANWELL:  The International Pediatric Multiple Sclerosis Study Group recently had an international consensus discussion with respect to monitoring disease activity and are working as a collective toward the concept of defining a standard interpretation of adequate disease control for given treatments. Standardized protocols for clinical evaluations and for MRI scan interpretation will be essential. Determining what constitutes “adequate treatment response”, both in terms of relapse frequency and frequency of new lesions on MRI will be important components to consider.

What have the MRI studies shown us about the brain volume in pediatric patients with MS?

DR. BANWELL:  There are several things that we have learned about the impact of MS in the brains of children and teenagers.

With respect to brain growth and brain volume, we have learned that at the time of a first attack, children and teenagers with MS already have brain volumes that are about one standard deviation below what you would expect for someone their age and sex.

The inner skull size is also reduced, which suggests that there has been a failure of head and skull growth even before the first attack.

Following identification of MS in a child, the subsequent serial MRI studies have shown that children with MS fail to have age-expected brain growth. We do not see the age-expected rate of growth in our pediatric patients.

Around age 16 to 17 is when our brain volumes are the largest in our lifetime, but our pediatric patients show brain atrophy or progressive loss of brain volume after age 15, a time when normal brain volumes are pretty stable for at least a decade.

When we age, there is a gradual rate of brain volume loss, but this has not been imaged yet in our pediatric patients with MS since we do not have serial studies of individuals who are 30 or 40 yet who had pediatric-onset MS.

What else have MRI studies shown?

DR. BANWELL:  Another point to add is that when we look at patients with pediatric-onset MS compared with those with adult-onset MS matched for disease duration, pediatric patients on average have higher T2 and T1 lesion volumes compared with adults. This suggests that despite their young age, pediatric-onset MS patients have had sufficient time to accrue subclinical disease/lesions and may have an accelerated rate of new lesion formation.

MRI and some of the newer more advanced MRI techniques are also informing on brain tissue integrity. In studies that examine whether the white matter highways in the brain or the pathways in the brain are normal, we find that in both pediatric-onset and adult-onset MS, even normal-appearing white matter is not normal. It is not as well structured as it should be compared with age- and sex-matched controls. Further, the myelin integrity or the structural alignment in the brain of our pediatric patients may not be normal.

I think that emphasizes to all of us that MS is much more than just multiple areas of “sclerosis”  or scarring, which is what MS actually means. It is indeed a disease that has a more widespread impact on the central nervous system,  beyond the very bright T2 lesions that we normally count and measure.

That is important because it speaks to the subsequent requirement that we think about when considering treatment for MS. Our goal is to not only suppress the acquisition of new lesions, which is the common metric for clinical trials, but we also think about brain protection, brain preservation, and brain repair, which, I think, is potentially the underlying substrate that is not yet fully addressed by the evolving treatment.

Brenda L. Banwell, MD, is Chief of the Division of Neurology at Children’s Hospital of Philadelphia and holder of the Grace R. Loeb Endowed Chair in Neurosciences. Dr. Banwell is an expert in pediatric-onset multiple sclerosis (MS) with a clinical focus on cognitive features, neuroimaging, T and B-cell autoimmunity studies, and studies of viral triggers. We spoke with Dr. Banwell to discuss the disease course of pediatric-onset MS and the impact of magnetic resonance imaging (MRI).

How does the disease course of pediatric-onset MS differ from that of adult-onset MS?

DR. BANWELL:  Pediatric-onset MS is almost universally a relapsing-remitting disease at onset. Primary progressive MS is typically not seen in children younger than 18 years of age.

Children with progressive disability from onset should be considered more likely to have either a mitochondrial disease, genetic leukodystrophy or other disorder. Multiple sclerosis would not be a consideration for a child with progressive disability at the beginning.

Secondary progressive MS does not appear to occur for most children during the first 10 years of disease. Retrospective cohort studies suggest that secondary progressive MS in patients with pediatric-onset MS likely takes, on average, at least 20 years to occur from onset.

However, we should remember that pediatric-onset MS patients are at risk for secondary progression when they are only 30 or 35 years of age, depending on when they experienced their first attack. With the availability of numerous MS therapies, we are optimistic that secondary progressive MS may now be less likely to occur, or may be delayed even further from onset.

How often are MRIs performed on children with MS?

DR. BANWELL:  The most pivotal MRI is the one that helps you confirm the diagnosis. It is ideally obtained very close to the first onset of symptoms. That MRI could include the orbits, brain, and spine, depending on the clinical symptoms.

Following the first MRI scan, most of us would image our patients approximately every 3 months in the first year. After the first year, we would typically image our patients at least every 6 months, until, if they have been stable for an extended period of time, we might move to annual imaging.

The frequency of MRI scanning is determined by clinical disease activity, treatment decisions, and the age of the child. For example, very young children may require repeated exposure to anesthetics in order to obtain an MRI. We might have to think strategically about how often to put them under that degree of anesthesia to obtain imaging. Many young children are able to lie still for MRI if the facility has the option for viewing a video during the scan.

How do those MRI results influence your treatment decisions for the pediatric patient?

DR. BANWELL:  The International Pediatric Multiple Sclerosis Study Group recently had an international consensus discussion with respect to monitoring disease activity and are working as a collective toward the concept of defining a standard interpretation of adequate disease control for given treatments. Standardized protocols for clinical evaluations and for MRI scan interpretation will be essential. Determining what constitutes “adequate treatment response”, both in terms of relapse frequency and frequency of new lesions on MRI will be important components to consider.

What have the MRI studies shown us about the brain volume in pediatric patients with MS?

DR. BANWELL:  There are several things that we have learned about the impact of MS in the brains of children and teenagers.

With respect to brain growth and brain volume, we have learned that at the time of a first attack, children and teenagers with MS already have brain volumes that are about one standard deviation below what you would expect for someone their age and sex.

The inner skull size is also reduced, which suggests that there has been a failure of head and skull growth even before the first attack.

Following identification of MS in a child, the subsequent serial MRI studies have shown that children with MS fail to have age-expected brain growth. We do not see the age-expected rate of growth in our pediatric patients.

Around age 16 to 17 is when our brain volumes are the largest in our lifetime, but our pediatric patients show brain atrophy or progressive loss of brain volume after age 15, a time when normal brain volumes are pretty stable for at least a decade.

When we age, there is a gradual rate of brain volume loss, but this has not been imaged yet in our pediatric patients with MS since we do not have serial studies of individuals who are 30 or 40 yet who had pediatric-onset MS.

What else have MRI studies shown?

DR. BANWELL:  Another point to add is that when we look at patients with pediatric-onset MS compared with those with adult-onset MS matched for disease duration, pediatric patients on average have higher T2 and T1 lesion volumes compared with adults. This suggests that despite their young age, pediatric-onset MS patients have had sufficient time to accrue subclinical disease/lesions and may have an accelerated rate of new lesion formation.

MRI and some of the newer more advanced MRI techniques are also informing on brain tissue integrity. In studies that examine whether the white matter highways in the brain or the pathways in the brain are normal, we find that in both pediatric-onset and adult-onset MS, even normal-appearing white matter is not normal. It is not as well structured as it should be compared with age- and sex-matched controls. Further, the myelin integrity or the structural alignment in the brain of our pediatric patients may not be normal.

I think that emphasizes to all of us that MS is much more than just multiple areas of “sclerosis”  or scarring, which is what MS actually means. It is indeed a disease that has a more widespread impact on the central nervous system,  beyond the very bright T2 lesions that we normally count and measure.

That is important because it speaks to the subsequent requirement that we think about when considering treatment for MS. Our goal is to not only suppress the acquisition of new lesions, which is the common metric for clinical trials, but we also think about brain protection, brain preservation, and brain repair, which, I think, is potentially the underlying substrate that is not yet fully addressed by the evolving treatment.

SEATTLE – From the 1999 identification of neuromyelitis optica (NMO) as a disease state distinct from multiple sclerosis and first diagnostic criteria to the present time, the progress made in the understanding of NMO has been continuous. At the annual meeting of the Consortium of Multiple Sclerosis Centers, Brian Weinshenker, MD, professor of neurology at the Mayo Clinic in Rochester, Minn., summarized some of the milestones in the timeline of NMO research.

These milestones include the 2004 identification of NMO-IgG, an autoantibody marker of NMO that distinguishes it from multiple sclerosis; the 2005 discovery that the antibody was reactive to aquaporin 4, the dominant CNS water channel and an astrocyte protein; further characterizations of NMO manifestations; the revised international panel diagnostic criteria in 2015; and the current phase 3 trials of three potential treatments for NMO – eculizumab, inebilizumab, and satralizumab.

Dr. Weinshenker reported the following disclosures: receiving royalties from the RSR Group, Oxford University, Hospices Civils de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen for a patent of NMO-IgG as a diagnostic test for NMO and related disorders; serving as an adjudication committee member for clinical trials in NMO being conducted by MedImmune and Alexion; and consulting for Chugai regarding a clinical trial for NMO.

[email protected]

SEATTLE – From the 1999 identification of neuromyelitis optica (NMO) as a disease state distinct from multiple sclerosis and first diagnostic criteria to the present time, the progress made in the understanding of NMO has been continuous. At the annual meeting of the Consortium of Multiple Sclerosis Centers, Brian Weinshenker, MD, professor of neurology at the Mayo Clinic in Rochester, Minn., summarized some of the milestones in the timeline of NMO research.

These milestones include the 2004 identification of NMO-IgG, an autoantibody marker of NMO that distinguishes it from multiple sclerosis; the 2005 discovery that the antibody was reactive to aquaporin 4, the dominant CNS water channel and an astrocyte protein; further characterizations of NMO manifestations; the revised international panel diagnostic criteria in 2015; and the current phase 3 trials of three potential treatments for NMO – eculizumab, inebilizumab, and satralizumab.

Dr. Weinshenker reported the following disclosures: receiving royalties from the RSR Group, Oxford University, Hospices Civils de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen for a patent of NMO-IgG as a diagnostic test for NMO and related disorders; serving as an adjudication committee member for clinical trials in NMO being conducted by MedImmune and Alexion; and consulting for Chugai regarding a clinical trial for NMO.

[email protected]

SEATTLE – From the 1999 identification of neuromyelitis optica (NMO) as a disease state distinct from multiple sclerosis and first diagnostic criteria to the present time, the progress made in the understanding of NMO has been continuous. At the annual meeting of the Consortium of Multiple Sclerosis Centers, Brian Weinshenker, MD, professor of neurology at the Mayo Clinic in Rochester, Minn., summarized some of the milestones in the timeline of NMO research.

These milestones include the 2004 identification of NMO-IgG, an autoantibody marker of NMO that distinguishes it from multiple sclerosis; the 2005 discovery that the antibody was reactive to aquaporin 4, the dominant CNS water channel and an astrocyte protein; further characterizations of NMO manifestations; the revised international panel diagnostic criteria in 2015; and the current phase 3 trials of three potential treatments for NMO – eculizumab, inebilizumab, and satralizumab.

Dr. Weinshenker reported the following disclosures: receiving royalties from the RSR Group, Oxford University, Hospices Civils de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen for a patent of NMO-IgG as a diagnostic test for NMO and related disorders; serving as an adjudication committee member for clinical trials in NMO being conducted by MedImmune and Alexion; and consulting for Chugai regarding a clinical trial for NMO.

[email protected]

SEATTLE – A new study finds that patients with both multiple sclerosis (MS) and restless legs syndrome (RLS) were more likely to suffer from self-perceived cognitive impairment. The results suggest that sleep dysfunction exacerbated by RLS could affect cognition in patients with MS, study lead author Katie L. Cederberg, CPT, a doctoral student in the department of physical therapy at the University of Alabama at Birmingham, said in an interview. She spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

“RLS severity did predict cognitive impairment,” she said. However, she added, “this is just a snapshot, and we need to do more research.”

Sleep problems, including RLS, are more common in patients with MS than in the general population. “Current research suggests that anywhere from 19% to 67% of individuals with MS experience some sort of sleep difficulty, with rates as high as 80% in some samples,” a 2015 report noted.

As for RLS, a 2018 systematic review and meta-analysis found that “pooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case-control studies (23%). RLS prevalence was higher among female than among male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (odds ratio, 3.96, 95% confidence interval, 3.29-4.77, P less than .001) (Sleep Med. 2018 Oct;50:97-104).

Ms. Cederberg said the frequency of RLS in patients with MS spurred her and colleagues to explore whether it may affect cognitive function.

For their study, the researchers surveyed 275 patients with MS (mean age = 60, 81% female, 33% employed, 95% white, 66% with relapsing-remitting MS). Of the 275, 75 appeared to have RLS. These patients were similar to the non-RLS patients in multiple areas, but they diverged in scores on the brief Multiple Sclerosis Neuropsychological Questionnaire, which measures self-perception of cognition.

Those with both MS and RLS scored 21.9 (± 11.7) on the test, while those with MS scored 18.0 (± 11.0), P = 0.023.

Analyses linked greater RLS severity to worse self-perceived cognitive impairment and sleep quality. “The diagnosis and treatment of RLS symptoms and other effectors of sleep quality could improve cognitive consequences of MS,” the authors concluded.

The National MS Society funded the study. The study authors reported no relevant disclosures.

SEATTLE – A new study finds that patients with both multiple sclerosis (MS) and restless legs syndrome (RLS) were more likely to suffer from self-perceived cognitive impairment. The results suggest that sleep dysfunction exacerbated by RLS could affect cognition in patients with MS, study lead author Katie L. Cederberg, CPT, a doctoral student in the department of physical therapy at the University of Alabama at Birmingham, said in an interview. She spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

“RLS severity did predict cognitive impairment,” she said. However, she added, “this is just a snapshot, and we need to do more research.”

Sleep problems, including RLS, are more common in patients with MS than in the general population. “Current research suggests that anywhere from 19% to 67% of individuals with MS experience some sort of sleep difficulty, with rates as high as 80% in some samples,” a 2015 report noted.

As for RLS, a 2018 systematic review and meta-analysis found that “pooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case-control studies (23%). RLS prevalence was higher among female than among male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (odds ratio, 3.96, 95% confidence interval, 3.29-4.77, P less than .001) (Sleep Med. 2018 Oct;50:97-104).

Ms. Cederberg said the frequency of RLS in patients with MS spurred her and colleagues to explore whether it may affect cognitive function.

For their study, the researchers surveyed 275 patients with MS (mean age = 60, 81% female, 33% employed, 95% white, 66% with relapsing-remitting MS). Of the 275, 75 appeared to have RLS. These patients were similar to the non-RLS patients in multiple areas, but they diverged in scores on the brief Multiple Sclerosis Neuropsychological Questionnaire, which measures self-perception of cognition.

Those with both MS and RLS scored 21.9 (± 11.7) on the test, while those with MS scored 18.0 (± 11.0), P = 0.023.

Analyses linked greater RLS severity to worse self-perceived cognitive impairment and sleep quality. “The diagnosis and treatment of RLS symptoms and other effectors of sleep quality could improve cognitive consequences of MS,” the authors concluded.

The National MS Society funded the study. The study authors reported no relevant disclosures.

SEATTLE – A new study finds that patients with both multiple sclerosis (MS) and restless legs syndrome (RLS) were more likely to suffer from self-perceived cognitive impairment. The results suggest that sleep dysfunction exacerbated by RLS could affect cognition in patients with MS, study lead author Katie L. Cederberg, CPT, a doctoral student in the department of physical therapy at the University of Alabama at Birmingham, said in an interview. She spoke at the annual meeting of the Consortium of Multiple Sclerosis Centers, where she presented the findings.

“RLS severity did predict cognitive impairment,” she said. However, she added, “this is just a snapshot, and we need to do more research.”

Sleep problems, including RLS, are more common in patients with MS than in the general population. “Current research suggests that anywhere from 19% to 67% of individuals with MS experience some sort of sleep difficulty, with rates as high as 80% in some samples,” a 2015 report noted.

As for RLS, a 2018 systematic review and meta-analysis found that “pooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case-control studies (23%). RLS prevalence was higher among female than among male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (odds ratio, 3.96, 95% confidence interval, 3.29-4.77, P less than .001) (Sleep Med. 2018 Oct;50:97-104).

Ms. Cederberg said the frequency of RLS in patients with MS spurred her and colleagues to explore whether it may affect cognitive function.

For their study, the researchers surveyed 275 patients with MS (mean age = 60, 81% female, 33% employed, 95% white, 66% with relapsing-remitting MS). Of the 275, 75 appeared to have RLS. These patients were similar to the non-RLS patients in multiple areas, but they diverged in scores on the brief Multiple Sclerosis Neuropsychological Questionnaire, which measures self-perception of cognition.

Those with both MS and RLS scored 21.9 (± 11.7) on the test, while those with MS scored 18.0 (± 11.0), P = 0.023.

Analyses linked greater RLS severity to worse self-perceived cognitive impairment and sleep quality. “The diagnosis and treatment of RLS symptoms and other effectors of sleep quality could improve cognitive consequences of MS,” the authors concluded.

The National MS Society funded the study. The study authors reported no relevant disclosures.