TBD Meeting (2962-18)

LOS ANGELES – Serum neurofilament light chain shows promise as a biomarker for disease severity and response to treatment with autologous bone marrow transplant in patients with multiple sclerosis, according to findings from an analysis of paired samples.

solitude72/iStockphoto

Serum neurofilament light chain (Nf-L) levels were found to be significantly elevated in both the serum and cerebrospinal fluid (CSF) of 23 patients with aggressive multiple sclerosis (MS), compared with samples from 5 controls with noninflammatory neurologic conditions such as chronic fatigue syndrome or migraine. The levels in the patients with MS were significantly reduced following autologous bone marrow transplant (BMT), Simon Thebault, MD, reported in a poster at the annual meeting of the American Academy of Neurology.

Nf-L has been shown to be a biomarker for neuronal damage and to have potential for denoting disease severity and treatment response in MS; for this analysis, samples from patients were collected at baseline and annually for 3 years after transplant. Samples from controls were obtained for comparison.

“Our objective, really, was [to determine if we could] detect a treatment response in neurofilament light chain, and secondly, did the degree of neurofilament light chain being high at baseline predict anything about subsequent disease outcome?” Dr. Thebault, a third-year resident at the University of Ottawa, reported in the poster.

Indeed, a treatment response was detected; baseline levels were high, and levels in both serum and CSF were down significantly (P = .05) at both 1 and 3 years following bone marrow transplant, and they stayed down. “In fact, they were so low, they were not significantly different from [the levels] in noninflammatory controls,” he said, noting that serum and CSF NfL levels were highly correlated (r = .833; P less than .001).

Study subjects were patients with aggressive MS, characterized by early disease onset, rapid progression, frequent relapses, and poor treatment responses. Such patients who have received autologous BMT represent an interesting group for examining treatment responses, he said.

At baseline, these patients presumably have a high burden of tissue injury, which would be representative of high levels of Nf-L; good, prospective data show these patients have no evidence of ongoing inflammatory disease following an intensive regimen that includes chemoablation and reinfusion of autologous stem cells, which is representative of a significant reduction of neurofilament levels, he explained.

Importantly, serum and CSF levels were correlated in this study, he said, noting that most prior work has involved CSF, but “the real clinical utility in neurofilament light chain is probably in the serum, because patients don’t like having lumbar punctures too often.”

With respect to the second question pertaining to disease outcomes, the study did show that patients with baseline Nf-L levels above the median for the group had worse T1 lesion volumes at baseline and after transplant (P = .0021 at 36 months), and also had worsening brain atrophy even after transplant (P = .0389 at 60 months).

The curves appeared to be diverging, suggesting that, in the absence of inflammatory disease activity, patients with high Nf-L levels at baseline continue to have ongoing atrophy at a differential rate, compared with those with low baseline levels, Dr. Thebault said.

Other findings included better Expanded Disability Status Scale outcomes after transplant in patients with lower baseline Nf-L, and a trend toward worsening outcomes among those with higher baseline Nf-L levels, although the study may have been underpowered for this. Additionally, lower baseline Nf-L predicted significantly lower T1 and T2 lesion volume, number of gadolinium-enhancing lesions, and a reduction in brain atrophy, whereas higher baseline Nf-L predicted the opposite, he noted, adding that N-acetylaspartate-to-creatinine ratios also tended to vary inversely with Nf-L levels.

The most important findings of the study are “the sustained reduction in Nf-L levels after BMT, and that higher baseline levels predicted worse MRI outcomes,” Dr. Thebault noted. “Together these data add to a growing body of evidence that suggests that serum Nf-L has a role in monitoring treatment responses and even a predictive value in determining disease severity.”

This study was supported by Quanterix, which provided Nf-L assay kits. Dr. Thebault reported having no disclosures.

[email protected]

SOURCE: Thebault S et al. Neurology. 2018 Apr;90(15 Suppl.):P5.036.

LOS ANGELES – Serum neurofilament light chain shows promise as a biomarker for disease severity and response to treatment with autologous bone marrow transplant in patients with multiple sclerosis, according to findings from an analysis of paired samples.

solitude72/iStockphoto

Serum neurofilament light chain (Nf-L) levels were found to be significantly elevated in both the serum and cerebrospinal fluid (CSF) of 23 patients with aggressive multiple sclerosis (MS), compared with samples from 5 controls with noninflammatory neurologic conditions such as chronic fatigue syndrome or migraine. The levels in the patients with MS were significantly reduced following autologous bone marrow transplant (BMT), Simon Thebault, MD, reported in a poster at the annual meeting of the American Academy of Neurology.

Nf-L has been shown to be a biomarker for neuronal damage and to have potential for denoting disease severity and treatment response in MS; for this analysis, samples from patients were collected at baseline and annually for 3 years after transplant. Samples from controls were obtained for comparison.

“Our objective, really, was [to determine if we could] detect a treatment response in neurofilament light chain, and secondly, did the degree of neurofilament light chain being high at baseline predict anything about subsequent disease outcome?” Dr. Thebault, a third-year resident at the University of Ottawa, reported in the poster.

Indeed, a treatment response was detected; baseline levels were high, and levels in both serum and CSF were down significantly (P = .05) at both 1 and 3 years following bone marrow transplant, and they stayed down. “In fact, they were so low, they were not significantly different from [the levels] in noninflammatory controls,” he said, noting that serum and CSF NfL levels were highly correlated (r = .833; P less than .001).

Study subjects were patients with aggressive MS, characterized by early disease onset, rapid progression, frequent relapses, and poor treatment responses. Such patients who have received autologous BMT represent an interesting group for examining treatment responses, he said.

At baseline, these patients presumably have a high burden of tissue injury, which would be representative of high levels of Nf-L; good, prospective data show these patients have no evidence of ongoing inflammatory disease following an intensive regimen that includes chemoablation and reinfusion of autologous stem cells, which is representative of a significant reduction of neurofilament levels, he explained.

Importantly, serum and CSF levels were correlated in this study, he said, noting that most prior work has involved CSF, but “the real clinical utility in neurofilament light chain is probably in the serum, because patients don’t like having lumbar punctures too often.”

With respect to the second question pertaining to disease outcomes, the study did show that patients with baseline Nf-L levels above the median for the group had worse T1 lesion volumes at baseline and after transplant (P = .0021 at 36 months), and also had worsening brain atrophy even after transplant (P = .0389 at 60 months).

The curves appeared to be diverging, suggesting that, in the absence of inflammatory disease activity, patients with high Nf-L levels at baseline continue to have ongoing atrophy at a differential rate, compared with those with low baseline levels, Dr. Thebault said.

Other findings included better Expanded Disability Status Scale outcomes after transplant in patients with lower baseline Nf-L, and a trend toward worsening outcomes among those with higher baseline Nf-L levels, although the study may have been underpowered for this. Additionally, lower baseline Nf-L predicted significantly lower T1 and T2 lesion volume, number of gadolinium-enhancing lesions, and a reduction in brain atrophy, whereas higher baseline Nf-L predicted the opposite, he noted, adding that N-acetylaspartate-to-creatinine ratios also tended to vary inversely with Nf-L levels.

The most important findings of the study are “the sustained reduction in Nf-L levels after BMT, and that higher baseline levels predicted worse MRI outcomes,” Dr. Thebault noted. “Together these data add to a growing body of evidence that suggests that serum Nf-L has a role in monitoring treatment responses and even a predictive value in determining disease severity.”

This study was supported by Quanterix, which provided Nf-L assay kits. Dr. Thebault reported having no disclosures.

[email protected]

SOURCE: Thebault S et al. Neurology. 2018 Apr;90(15 Suppl.):P5.036.

LOS ANGELES – Serum neurofilament light chain shows promise as a biomarker for disease severity and response to treatment with autologous bone marrow transplant in patients with multiple sclerosis, according to findings from an analysis of paired samples.

solitude72/iStockphoto

Serum neurofilament light chain (Nf-L) levels were found to be significantly elevated in both the serum and cerebrospinal fluid (CSF) of 23 patients with aggressive multiple sclerosis (MS), compared with samples from 5 controls with noninflammatory neurologic conditions such as chronic fatigue syndrome or migraine. The levels in the patients with MS were significantly reduced following autologous bone marrow transplant (BMT), Simon Thebault, MD, reported in a poster at the annual meeting of the American Academy of Neurology.

Nf-L has been shown to be a biomarker for neuronal damage and to have potential for denoting disease severity and treatment response in MS; for this analysis, samples from patients were collected at baseline and annually for 3 years after transplant. Samples from controls were obtained for comparison.

“Our objective, really, was [to determine if we could] detect a treatment response in neurofilament light chain, and secondly, did the degree of neurofilament light chain being high at baseline predict anything about subsequent disease outcome?” Dr. Thebault, a third-year resident at the University of Ottawa, reported in the poster.

Indeed, a treatment response was detected; baseline levels were high, and levels in both serum and CSF were down significantly (P = .05) at both 1 and 3 years following bone marrow transplant, and they stayed down. “In fact, they were so low, they were not significantly different from [the levels] in noninflammatory controls,” he said, noting that serum and CSF NfL levels were highly correlated (r = .833; P less than .001).

Study subjects were patients with aggressive MS, characterized by early disease onset, rapid progression, frequent relapses, and poor treatment responses. Such patients who have received autologous BMT represent an interesting group for examining treatment responses, he said.

At baseline, these patients presumably have a high burden of tissue injury, which would be representative of high levels of Nf-L; good, prospective data show these patients have no evidence of ongoing inflammatory disease following an intensive regimen that includes chemoablation and reinfusion of autologous stem cells, which is representative of a significant reduction of neurofilament levels, he explained.

Importantly, serum and CSF levels were correlated in this study, he said, noting that most prior work has involved CSF, but “the real clinical utility in neurofilament light chain is probably in the serum, because patients don’t like having lumbar punctures too often.”

With respect to the second question pertaining to disease outcomes, the study did show that patients with baseline Nf-L levels above the median for the group had worse T1 lesion volumes at baseline and after transplant (P = .0021 at 36 months), and also had worsening brain atrophy even after transplant (P = .0389 at 60 months).

The curves appeared to be diverging, suggesting that, in the absence of inflammatory disease activity, patients with high Nf-L levels at baseline continue to have ongoing atrophy at a differential rate, compared with those with low baseline levels, Dr. Thebault said.

Other findings included better Expanded Disability Status Scale outcomes after transplant in patients with lower baseline Nf-L, and a trend toward worsening outcomes among those with higher baseline Nf-L levels, although the study may have been underpowered for this. Additionally, lower baseline Nf-L predicted significantly lower T1 and T2 lesion volume, number of gadolinium-enhancing lesions, and a reduction in brain atrophy, whereas higher baseline Nf-L predicted the opposite, he noted, adding that N-acetylaspartate-to-creatinine ratios also tended to vary inversely with Nf-L levels.

The most important findings of the study are “the sustained reduction in Nf-L levels after BMT, and that higher baseline levels predicted worse MRI outcomes,” Dr. Thebault noted. “Together these data add to a growing body of evidence that suggests that serum Nf-L has a role in monitoring treatment responses and even a predictive value in determining disease severity.”

This study was supported by Quanterix, which provided Nf-L assay kits. Dr. Thebault reported having no disclosures.

[email protected]

SOURCE: Thebault S et al. Neurology. 2018 Apr;90(15 Suppl.):P5.036.

LOS ANGELES – A novel scoring system based on six readily available seizure risk factors from a patient’s history and continuous electroencephalogram (cEEG) monitoring appears to accurately predict seizures in acutely ill hospitalized patients.

The final model of the system, dubbed the 2HELPS2B score, has an area under the curve (AUC) of 0.821, suggesting a “good overall fit,” Aaron Struck, MD, reported at the annual meeting of the American Academy of Neurology.

However, more relevant than the AUC and suggestive of high classification accuracy is the low calibration error of 2.7%, which shows that the actual incidence of seizures within a particular risk group is, on average, within 2.7% of predicted incidence, Dr. Struck of the University of Wisconsin, Madison, explained in an interview.

The use of cEEG has expanded, largely because of a high incidence of subclinical seizures in hospitalized patients with encephalopathy; EEG features believed to predict seizures include epileptiform discharges and periodic discharges, but the ways in which these variables may jointly affect seizure risk have not been studied, he said.

He and his colleagues used a prospective database to derive a dataset containing 24 clinical and electroencephalographic variables for 5,427 cEEG sessions of at least 24 hours each, and then, using a machine-learning method known as RiskSLIM, created a scoring system model to estimate seizure risk in patients undergoing cEEG.

The name of the scoring system – 2HELPS2B – represents the six variables included in the final model:

• 2 H is for frequency greater than 2.0 Hz for any periodic rhythmic pattern (1 point).
• E is for sporadic epileptiform discharges (1 point).
• L is for the presence of lateralized periodic discharges, lateralized rhythmic delta activity, or bilateral independent periodic discharges (1 point).
• P is for the presence of “plus” features, including superimposed, rhythmic, sharp, or fast activity (1 point).
• S is for prior seizure (1 point).
• 2B is for brief, potentially ictal, rhythmic discharges (2 points).

The predicted seizure risk rose with score, such that the seizure risk was less than 5% for a score of 0, 12% for 1, 27% for 2, 50% for 3, 73% for 4, 88% for 5, and greater than 95% for 6-7, Dr. Struck said. “Really, anything over 2 points, you’re at substantial risk for having seizures.”

Limitations of the study, which are being addressed in an ongoing, multicenter, prospective validation trial through the Critical Care EEG Monitoring Research Consortium, are mainly related to the constraints of the database; the duration of EEG needed to accurately calculate the 2HELPS2B score wasn’t defined, and cEEGs were of varying length.

“So in our validation study moving forward, these are two things we will address,” he said. “We also want to show that this is something that’s useful on a day-to-day basis – that it accurately gauges the degree of variability or potential severity of the ictal-interictal continuum pattern.”

With validation, Dr. Struck said that the 2HELPS2B score could ultimately be used to rapidly communicate seizure potential based on EEG severity and to guide decision making with respect to initiation of empiric antiseizure medication.

Findings from the validation study are “trending in the right direction,” but the confidence intervals are wide, as only 404 patients have been included at this point, Dr. Struck said.

This study was supported by a research infrastructure award from the American Epilepsy Society and the Epilepsy Foundation.

[email protected]

SOURCE: Struck A et al. Neurology. 2018 Apr 90(15 Suppl.):S11.002.

LOS ANGELES – A novel scoring system based on six readily available seizure risk factors from a patient’s history and continuous electroencephalogram (cEEG) monitoring appears to accurately predict seizures in acutely ill hospitalized patients.

The final model of the system, dubbed the 2HELPS2B score, has an area under the curve (AUC) of 0.821, suggesting a “good overall fit,” Aaron Struck, MD, reported at the annual meeting of the American Academy of Neurology.

However, more relevant than the AUC and suggestive of high classification accuracy is the low calibration error of 2.7%, which shows that the actual incidence of seizures within a particular risk group is, on average, within 2.7% of predicted incidence, Dr. Struck of the University of Wisconsin, Madison, explained in an interview.

The use of cEEG has expanded, largely because of a high incidence of subclinical seizures in hospitalized patients with encephalopathy; EEG features believed to predict seizures include epileptiform discharges and periodic discharges, but the ways in which these variables may jointly affect seizure risk have not been studied, he said.

He and his colleagues used a prospective database to derive a dataset containing 24 clinical and electroencephalographic variables for 5,427 cEEG sessions of at least 24 hours each, and then, using a machine-learning method known as RiskSLIM, created a scoring system model to estimate seizure risk in patients undergoing cEEG.

The name of the scoring system – 2HELPS2B – represents the six variables included in the final model:

• 2 H is for frequency greater than 2.0 Hz for any periodic rhythmic pattern (1 point).
• E is for sporadic epileptiform discharges (1 point).
• L is for the presence of lateralized periodic discharges, lateralized rhythmic delta activity, or bilateral independent periodic discharges (1 point).
• P is for the presence of “plus” features, including superimposed, rhythmic, sharp, or fast activity (1 point).
• S is for prior seizure (1 point).
• 2B is for brief, potentially ictal, rhythmic discharges (2 points).

The predicted seizure risk rose with score, such that the seizure risk was less than 5% for a score of 0, 12% for 1, 27% for 2, 50% for 3, 73% for 4, 88% for 5, and greater than 95% for 6-7, Dr. Struck said. “Really, anything over 2 points, you’re at substantial risk for having seizures.”

Limitations of the study, which are being addressed in an ongoing, multicenter, prospective validation trial through the Critical Care EEG Monitoring Research Consortium, are mainly related to the constraints of the database; the duration of EEG needed to accurately calculate the 2HELPS2B score wasn’t defined, and cEEGs were of varying length.

“So in our validation study moving forward, these are two things we will address,” he said. “We also want to show that this is something that’s useful on a day-to-day basis – that it accurately gauges the degree of variability or potential severity of the ictal-interictal continuum pattern.”

With validation, Dr. Struck said that the 2HELPS2B score could ultimately be used to rapidly communicate seizure potential based on EEG severity and to guide decision making with respect to initiation of empiric antiseizure medication.

Findings from the validation study are “trending in the right direction,” but the confidence intervals are wide, as only 404 patients have been included at this point, Dr. Struck said.

This study was supported by a research infrastructure award from the American Epilepsy Society and the Epilepsy Foundation.

[email protected]

SOURCE: Struck A et al. Neurology. 2018 Apr 90(15 Suppl.):S11.002.

LOS ANGELES – A novel scoring system based on six readily available seizure risk factors from a patient’s history and continuous electroencephalogram (cEEG) monitoring appears to accurately predict seizures in acutely ill hospitalized patients.

The final model of the system, dubbed the 2HELPS2B score, has an area under the curve (AUC) of 0.821, suggesting a “good overall fit,” Aaron Struck, MD, reported at the annual meeting of the American Academy of Neurology.

However, more relevant than the AUC and suggestive of high classification accuracy is the low calibration error of 2.7%, which shows that the actual incidence of seizures within a particular risk group is, on average, within 2.7% of predicted incidence, Dr. Struck of the University of Wisconsin, Madison, explained in an interview.

The use of cEEG has expanded, largely because of a high incidence of subclinical seizures in hospitalized patients with encephalopathy; EEG features believed to predict seizures include epileptiform discharges and periodic discharges, but the ways in which these variables may jointly affect seizure risk have not been studied, he said.

He and his colleagues used a prospective database to derive a dataset containing 24 clinical and electroencephalographic variables for 5,427 cEEG sessions of at least 24 hours each, and then, using a machine-learning method known as RiskSLIM, created a scoring system model to estimate seizure risk in patients undergoing cEEG.

The name of the scoring system – 2HELPS2B – represents the six variables included in the final model:

• 2 H is for frequency greater than 2.0 Hz for any periodic rhythmic pattern (1 point).
• E is for sporadic epileptiform discharges (1 point).
• L is for the presence of lateralized periodic discharges, lateralized rhythmic delta activity, or bilateral independent periodic discharges (1 point).
• P is for the presence of “plus” features, including superimposed, rhythmic, sharp, or fast activity (1 point).
• S is for prior seizure (1 point).
• 2B is for brief, potentially ictal, rhythmic discharges (2 points).

The predicted seizure risk rose with score, such that the seizure risk was less than 5% for a score of 0, 12% for 1, 27% for 2, 50% for 3, 73% for 4, 88% for 5, and greater than 95% for 6-7, Dr. Struck said. “Really, anything over 2 points, you’re at substantial risk for having seizures.”

Limitations of the study, which are being addressed in an ongoing, multicenter, prospective validation trial through the Critical Care EEG Monitoring Research Consortium, are mainly related to the constraints of the database; the duration of EEG needed to accurately calculate the 2HELPS2B score wasn’t defined, and cEEGs were of varying length.

“So in our validation study moving forward, these are two things we will address,” he said. “We also want to show that this is something that’s useful on a day-to-day basis – that it accurately gauges the degree of variability or potential severity of the ictal-interictal continuum pattern.”

With validation, Dr. Struck said that the 2HELPS2B score could ultimately be used to rapidly communicate seizure potential based on EEG severity and to guide decision making with respect to initiation of empiric antiseizure medication.

Findings from the validation study are “trending in the right direction,” but the confidence intervals are wide, as only 404 patients have been included at this point, Dr. Struck said.

This study was supported by a research infrastructure award from the American Epilepsy Society and the Epilepsy Foundation.

[email protected]

SOURCE: Struck A et al. Neurology. 2018 Apr 90(15 Suppl.):S11.002.

LOS ANGELES – The commercially available Fitbit Flex accelerometer proved useful and feasible for longitudinal measurement of average daily steps in a prospective, 1-year study of patients with multiple sclerosis.

The wrist-worn device was well received, with 79 of 96 participants (82%) completing follow-up, and it revealed changes in daily functioning that were not captured using more traditional disability metrics, Valerie J. Block, DPTSc, reported at the annual meeting of the American Academy of Neurology.

The study involved 61 adults with relapsing multiple sclerosis (MS) and 35 with progressive MS who were recruited into the University of California, San Francisco (UCSF) FITriMS cohort. All were able to walk at least 2 minutes at baseline, and their daily physical activity was recorded continuously by the device over 1 year. Performance-based measures, including the Expanded Disability Status Scale (EDSS) and timed 25-foot walk test, were evaluated at baseline and at 1 year, and patient-reported outcomes such as the 12-item MS walking scale were completed at baseline and at 1.5, 3, 6, 9, and 12 months. Nine patients withdrew, and eight were lost to follow-up.

“This was a fairly stable, actively treated cohort, and overall, there was no significant change in average daily steps (STEPS) over 1 year. However, there was a trend toward a decrease (–315 steps/day; P = .117), and 53% of patients had a decrease of more than 800 steps per day, which is a proposed minimal clinically important difference threshold,” Dr. Block, a postdoctoral scholar at UCSF, said in an interview.

Despite the modest, gradual reduction in STEPS over the year, most participants were able to complete the study, providing at least 1 valid week of STEPS data per month throughout the year, she said, noting that there was no difference in device use between relapsing MS and progressive MS participants.

A significant association between decreasing STEPS and worsening of clinic-based and patient-reported outcomes was demonstrated, but declining STEPS occurred even when disability levels, as measured by the EDSS, remained stable.

“Participants who started off the study with lower STEPS, below the cohort median of 4,766 STEPS, had fourfold higher odds of clinically-meaningful disability worsening at 1 year after adjusting for age, sex, and disease duration,” she said.

Further, earlier data published by Dr. Block and her colleagues showed there is wide variability in the change in steps over 1 year. In that study, the change in step count in patients whose EDSS score remained unchanged ranged from +814 to –3,718, suggesting that popular mainstream wearable technology is not only feasible but also can provide a more detailed and nuanced measure of how patients are functioning in their daily lives, she said.

Together, these findings suggest that remote accelerometry provides useful continuous information about physical activity in real-world setting, she said, concluding that “these results support the possibility of using STEPS as a more sensitive and granular outcome measure in clinical trials and for targeted interventions in clinical care.”

This study was supported by the National Center for Advancing Translational Sciences. Dr. Block reported having no disclosures.

[email protected]

SOURCE: Block VJ et al. Neurology. 2018 Apr 10;90(15 Suppl):N5.001.

LOS ANGELES – The commercially available Fitbit Flex accelerometer proved useful and feasible for longitudinal measurement of average daily steps in a prospective, 1-year study of patients with multiple sclerosis.

The wrist-worn device was well received, with 79 of 96 participants (82%) completing follow-up, and it revealed changes in daily functioning that were not captured using more traditional disability metrics, Valerie J. Block, DPTSc, reported at the annual meeting of the American Academy of Neurology.

The study involved 61 adults with relapsing multiple sclerosis (MS) and 35 with progressive MS who were recruited into the University of California, San Francisco (UCSF) FITriMS cohort. All were able to walk at least 2 minutes at baseline, and their daily physical activity was recorded continuously by the device over 1 year. Performance-based measures, including the Expanded Disability Status Scale (EDSS) and timed 25-foot walk test, were evaluated at baseline and at 1 year, and patient-reported outcomes such as the 12-item MS walking scale were completed at baseline and at 1.5, 3, 6, 9, and 12 months. Nine patients withdrew, and eight were lost to follow-up.

“This was a fairly stable, actively treated cohort, and overall, there was no significant change in average daily steps (STEPS) over 1 year. However, there was a trend toward a decrease (–315 steps/day; P = .117), and 53% of patients had a decrease of more than 800 steps per day, which is a proposed minimal clinically important difference threshold,” Dr. Block, a postdoctoral scholar at UCSF, said in an interview.

Despite the modest, gradual reduction in STEPS over the year, most participants were able to complete the study, providing at least 1 valid week of STEPS data per month throughout the year, she said, noting that there was no difference in device use between relapsing MS and progressive MS participants.

A significant association between decreasing STEPS and worsening of clinic-based and patient-reported outcomes was demonstrated, but declining STEPS occurred even when disability levels, as measured by the EDSS, remained stable.

“Participants who started off the study with lower STEPS, below the cohort median of 4,766 STEPS, had fourfold higher odds of clinically-meaningful disability worsening at 1 year after adjusting for age, sex, and disease duration,” she said.

Further, earlier data published by Dr. Block and her colleagues showed there is wide variability in the change in steps over 1 year. In that study, the change in step count in patients whose EDSS score remained unchanged ranged from +814 to –3,718, suggesting that popular mainstream wearable technology is not only feasible but also can provide a more detailed and nuanced measure of how patients are functioning in their daily lives, she said.

Together, these findings suggest that remote accelerometry provides useful continuous information about physical activity in real-world setting, she said, concluding that “these results support the possibility of using STEPS as a more sensitive and granular outcome measure in clinical trials and for targeted interventions in clinical care.”

This study was supported by the National Center for Advancing Translational Sciences. Dr. Block reported having no disclosures.

[email protected]

SOURCE: Block VJ et al. Neurology. 2018 Apr 10;90(15 Suppl):N5.001.

LOS ANGELES – The commercially available Fitbit Flex accelerometer proved useful and feasible for longitudinal measurement of average daily steps in a prospective, 1-year study of patients with multiple sclerosis.

The wrist-worn device was well received, with 79 of 96 participants (82%) completing follow-up, and it revealed changes in daily functioning that were not captured using more traditional disability metrics, Valerie J. Block, DPTSc, reported at the annual meeting of the American Academy of Neurology.

The study involved 61 adults with relapsing multiple sclerosis (MS) and 35 with progressive MS who were recruited into the University of California, San Francisco (UCSF) FITriMS cohort. All were able to walk at least 2 minutes at baseline, and their daily physical activity was recorded continuously by the device over 1 year. Performance-based measures, including the Expanded Disability Status Scale (EDSS) and timed 25-foot walk test, were evaluated at baseline and at 1 year, and patient-reported outcomes such as the 12-item MS walking scale were completed at baseline and at 1.5, 3, 6, 9, and 12 months. Nine patients withdrew, and eight were lost to follow-up.

“This was a fairly stable, actively treated cohort, and overall, there was no significant change in average daily steps (STEPS) over 1 year. However, there was a trend toward a decrease (–315 steps/day; P = .117), and 53% of patients had a decrease of more than 800 steps per day, which is a proposed minimal clinically important difference threshold,” Dr. Block, a postdoctoral scholar at UCSF, said in an interview.

Despite the modest, gradual reduction in STEPS over the year, most participants were able to complete the study, providing at least 1 valid week of STEPS data per month throughout the year, she said, noting that there was no difference in device use between relapsing MS and progressive MS participants.

A significant association between decreasing STEPS and worsening of clinic-based and patient-reported outcomes was demonstrated, but declining STEPS occurred even when disability levels, as measured by the EDSS, remained stable.

“Participants who started off the study with lower STEPS, below the cohort median of 4,766 STEPS, had fourfold higher odds of clinically-meaningful disability worsening at 1 year after adjusting for age, sex, and disease duration,” she said.

Further, earlier data published by Dr. Block and her colleagues showed there is wide variability in the change in steps over 1 year. In that study, the change in step count in patients whose EDSS score remained unchanged ranged from +814 to –3,718, suggesting that popular mainstream wearable technology is not only feasible but also can provide a more detailed and nuanced measure of how patients are functioning in their daily lives, she said.

Together, these findings suggest that remote accelerometry provides useful continuous information about physical activity in real-world setting, she said, concluding that “these results support the possibility of using STEPS as a more sensitive and granular outcome measure in clinical trials and for targeted interventions in clinical care.”

This study was supported by the National Center for Advancing Translational Sciences. Dr. Block reported having no disclosures.

[email protected]

SOURCE: Block VJ et al. Neurology. 2018 Apr 10;90(15 Suppl):N5.001.

LOS ANGELES – The more severe retinopathy is at midlife, the greater the risk of ischemic stroke – particularly lacunar stroke – later on, according to investigators from Johns Hopkins University, Baltimore.

Retinopathy has been associated with strokes before, but the investigators wanted to see whether it could predict stroke type. The idea is that microvascular changes in the retina could mirror microvascular changes in the brain that could lead to stroke.

The positive findings mean that “retinal microvasculature may serve as a biomarker for cerebrovascular health. Retinal imaging may enable further risk stratification of cerebrovascular and neurodegenerative diseases for early, intensive preventive interventions,” said lead investigator Michelle Lin, MD, a stroke fellow at Johns Hopkins.

A full evaluation is beyond the scope of a quick ophthalmoscope check up in the office. The advent of smartphone fundoscopic cameras and optical coherence tomography – which provides images of retinal vasculature at micrometer-level resolution – will likely help retinal imaging reach its full potential in the clinic, she said at the annual meeting of the American Academy of Neurology.

Dr. Lin and her team reviewed 10,468 participants in the Atherosclerosis Risk in Communities Study database. They had baseline retinal photographs from 1993-1995 when they were 45-65 years old. The photos were checked for four types of retinopathy: arteriovenous nicking, focal arteriolar narrowing, retinal microaneurysms, and retinal hemorrhage. The presence of each one was given a score of 1, yielding a retinopathy severity score of 0-4, with 4 meaning subjects had all four types.

Over a median follow-up period of 18.8 years, 578 participants had an ischemic stroke, including 114 lacunar strokes, 292 nonlacunar strokes, and 172 cardioembolic strokes. Hemorrhagic strokes occurred in 95 subjects.

The incidence of ischemic stroke increased with the severity of baseline retinopathy, from 2.7 strokes per 1,000 participant-years among those with no retinopathy to 10.2 among those with a severity score of 3 or higher (P less than .001). The 15-year cumulative risk of ischemic stroke with any retinopathy was 3.4% versus 1.6% with no retinopathy (P less than .001).

After adjustment for age, sex, race, comorbidities, and other confounders, retinal microvasculopathy associated positively with ischemic stroke, especially lacunar stroke (adjusted hazard ratio, 1.84; 95% confidence interval, 1.23-2.74; P = .005).

Trends linking retinopathy severity to the incidence of nonlacunar, cardioembolic, and hemorrhagic strokes were not statistically significant. Factors associated with higher retinopathy grade included older age, black race, hypertension, and diabetes, among others.

There were slightly more women than men in the review. The average age at baseline was 59 years. Patients with stroke histories at baseline were excluded.

The work was funded by the National Institutes of Health. The investigators had no disclosures.
 

[email protected]

SOURCE: Lin MP et al. Neurology. 2018 Apr;90(15 Suppl.):CCI.001.

LOS ANGELES – The more severe retinopathy is at midlife, the greater the risk of ischemic stroke – particularly lacunar stroke – later on, according to investigators from Johns Hopkins University, Baltimore.

Retinopathy has been associated with strokes before, but the investigators wanted to see whether it could predict stroke type. The idea is that microvascular changes in the retina could mirror microvascular changes in the brain that could lead to stroke.

The positive findings mean that “retinal microvasculature may serve as a biomarker for cerebrovascular health. Retinal imaging may enable further risk stratification of cerebrovascular and neurodegenerative diseases for early, intensive preventive interventions,” said lead investigator Michelle Lin, MD, a stroke fellow at Johns Hopkins.

A full evaluation is beyond the scope of a quick ophthalmoscope check up in the office. The advent of smartphone fundoscopic cameras and optical coherence tomography – which provides images of retinal vasculature at micrometer-level resolution – will likely help retinal imaging reach its full potential in the clinic, she said at the annual meeting of the American Academy of Neurology.

Dr. Lin and her team reviewed 10,468 participants in the Atherosclerosis Risk in Communities Study database. They had baseline retinal photographs from 1993-1995 when they were 45-65 years old. The photos were checked for four types of retinopathy: arteriovenous nicking, focal arteriolar narrowing, retinal microaneurysms, and retinal hemorrhage. The presence of each one was given a score of 1, yielding a retinopathy severity score of 0-4, with 4 meaning subjects had all four types.

Over a median follow-up period of 18.8 years, 578 participants had an ischemic stroke, including 114 lacunar strokes, 292 nonlacunar strokes, and 172 cardioembolic strokes. Hemorrhagic strokes occurred in 95 subjects.

The incidence of ischemic stroke increased with the severity of baseline retinopathy, from 2.7 strokes per 1,000 participant-years among those with no retinopathy to 10.2 among those with a severity score of 3 or higher (P less than .001). The 15-year cumulative risk of ischemic stroke with any retinopathy was 3.4% versus 1.6% with no retinopathy (P less than .001).

After adjustment for age, sex, race, comorbidities, and other confounders, retinal microvasculopathy associated positively with ischemic stroke, especially lacunar stroke (adjusted hazard ratio, 1.84; 95% confidence interval, 1.23-2.74; P = .005).

Trends linking retinopathy severity to the incidence of nonlacunar, cardioembolic, and hemorrhagic strokes were not statistically significant. Factors associated with higher retinopathy grade included older age, black race, hypertension, and diabetes, among others.

There were slightly more women than men in the review. The average age at baseline was 59 years. Patients with stroke histories at baseline were excluded.

The work was funded by the National Institutes of Health. The investigators had no disclosures.
 

[email protected]

SOURCE: Lin MP et al. Neurology. 2018 Apr;90(15 Suppl.):CCI.001.

LOS ANGELES – The more severe retinopathy is at midlife, the greater the risk of ischemic stroke – particularly lacunar stroke – later on, according to investigators from Johns Hopkins University, Baltimore.

Retinopathy has been associated with strokes before, but the investigators wanted to see whether it could predict stroke type. The idea is that microvascular changes in the retina could mirror microvascular changes in the brain that could lead to stroke.

The positive findings mean that “retinal microvasculature may serve as a biomarker for cerebrovascular health. Retinal imaging may enable further risk stratification of cerebrovascular and neurodegenerative diseases for early, intensive preventive interventions,” said lead investigator Michelle Lin, MD, a stroke fellow at Johns Hopkins.

A full evaluation is beyond the scope of a quick ophthalmoscope check up in the office. The advent of smartphone fundoscopic cameras and optical coherence tomography – which provides images of retinal vasculature at micrometer-level resolution – will likely help retinal imaging reach its full potential in the clinic, she said at the annual meeting of the American Academy of Neurology.

Dr. Lin and her team reviewed 10,468 participants in the Atherosclerosis Risk in Communities Study database. They had baseline retinal photographs from 1993-1995 when they were 45-65 years old. The photos were checked for four types of retinopathy: arteriovenous nicking, focal arteriolar narrowing, retinal microaneurysms, and retinal hemorrhage. The presence of each one was given a score of 1, yielding a retinopathy severity score of 0-4, with 4 meaning subjects had all four types.

Over a median follow-up period of 18.8 years, 578 participants had an ischemic stroke, including 114 lacunar strokes, 292 nonlacunar strokes, and 172 cardioembolic strokes. Hemorrhagic strokes occurred in 95 subjects.

The incidence of ischemic stroke increased with the severity of baseline retinopathy, from 2.7 strokes per 1,000 participant-years among those with no retinopathy to 10.2 among those with a severity score of 3 or higher (P less than .001). The 15-year cumulative risk of ischemic stroke with any retinopathy was 3.4% versus 1.6% with no retinopathy (P less than .001).

After adjustment for age, sex, race, comorbidities, and other confounders, retinal microvasculopathy associated positively with ischemic stroke, especially lacunar stroke (adjusted hazard ratio, 1.84; 95% confidence interval, 1.23-2.74; P = .005).

Trends linking retinopathy severity to the incidence of nonlacunar, cardioembolic, and hemorrhagic strokes were not statistically significant. Factors associated with higher retinopathy grade included older age, black race, hypertension, and diabetes, among others.

There were slightly more women than men in the review. The average age at baseline was 59 years. Patients with stroke histories at baseline were excluded.

The work was funded by the National Institutes of Health. The investigators had no disclosures.
 

[email protected]

SOURCE: Lin MP et al. Neurology. 2018 Apr;90(15 Suppl.):CCI.001.

LOS ANGELES – Patients with multiple sclerosis in the CARE-MS II study who switched from interferon beta-1a therapy to the humanized monoclonal antibody alemtuzumab experienced continued reductions in brain volume loss and lesions on MRI through 5 years, according to follow-up data from the CARE-MS II extension study known as TOPAZ.

These outcomes support core findings from the CARE-MS II study, and suggest that alemtuzumab (Lemtrada) provides a unique treatment approach for patients with prior subcutaneous interferon beta-1a (IFNB-1a) treatment, Daniel Pelletier, MD, reported in a poster discussion session at the annual meeting of the American Academy of Neurology.

In CARE-MS II, relapsing-remitting multiple sclerosis patients with inadequate response to prior therapy experienced improvements in MRI lesions and brain volume loss with two courses of alemtuzumab versus IFNB-1a through 2 years, and in a 4-year extension in which participants discontinued subcutaneous IFNB-1a and initiated alemtuzumab at 12 mg/day, they experienced durable efficacy in the absence of continuous treatment, explained Dr. Pelletier, a professor of neurology at the University of Southern California, Los Angeles.

In the extension, patients could receive alemtuzumab retreatment as needed for relapse/MRI activity or receive other disease-modifying therapies at the investigator’s discretion. Patients completing the extension could enter the 5-year TOPAZ study for further evaluation, he said.

Of 119 patients who completed TOPAZ year 1, and thus had 5 years of follow-up after initiating alemtuzumab, 78% were free of new, gadolinium-enhancing lesions in IFNB-1a year 2; this increased significantly to 92% in post-alemtuzumab year 2, and remained high at 85%-89% in years 3-5. Additionally, 48% of patients were free of new/enlarging T2 lesions in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2 and remained high in years 3-5.

Further, 47% of the TOPAZ patients were MRI disease activity–free in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2, and remained high at 67%-72% in years 3-5.

[email protected]

SOURCE: Pelletier D et al. Neurology. 2018 Apr 10. 90(15 Suppl.):P5.031.

LOS ANGELES – Patients with multiple sclerosis in the CARE-MS II study who switched from interferon beta-1a therapy to the humanized monoclonal antibody alemtuzumab experienced continued reductions in brain volume loss and lesions on MRI through 5 years, according to follow-up data from the CARE-MS II extension study known as TOPAZ.

These outcomes support core findings from the CARE-MS II study, and suggest that alemtuzumab (Lemtrada) provides a unique treatment approach for patients with prior subcutaneous interferon beta-1a (IFNB-1a) treatment, Daniel Pelletier, MD, reported in a poster discussion session at the annual meeting of the American Academy of Neurology.

In CARE-MS II, relapsing-remitting multiple sclerosis patients with inadequate response to prior therapy experienced improvements in MRI lesions and brain volume loss with two courses of alemtuzumab versus IFNB-1a through 2 years, and in a 4-year extension in which participants discontinued subcutaneous IFNB-1a and initiated alemtuzumab at 12 mg/day, they experienced durable efficacy in the absence of continuous treatment, explained Dr. Pelletier, a professor of neurology at the University of Southern California, Los Angeles.

In the extension, patients could receive alemtuzumab retreatment as needed for relapse/MRI activity or receive other disease-modifying therapies at the investigator’s discretion. Patients completing the extension could enter the 5-year TOPAZ study for further evaluation, he said.

Of 119 patients who completed TOPAZ year 1, and thus had 5 years of follow-up after initiating alemtuzumab, 78% were free of new, gadolinium-enhancing lesions in IFNB-1a year 2; this increased significantly to 92% in post-alemtuzumab year 2, and remained high at 85%-89% in years 3-5. Additionally, 48% of patients were free of new/enlarging T2 lesions in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2 and remained high in years 3-5.

Further, 47% of the TOPAZ patients were MRI disease activity–free in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2, and remained high at 67%-72% in years 3-5.

[email protected]

SOURCE: Pelletier D et al. Neurology. 2018 Apr 10. 90(15 Suppl.):P5.031.

LOS ANGELES – Patients with multiple sclerosis in the CARE-MS II study who switched from interferon beta-1a therapy to the humanized monoclonal antibody alemtuzumab experienced continued reductions in brain volume loss and lesions on MRI through 5 years, according to follow-up data from the CARE-MS II extension study known as TOPAZ.

These outcomes support core findings from the CARE-MS II study, and suggest that alemtuzumab (Lemtrada) provides a unique treatment approach for patients with prior subcutaneous interferon beta-1a (IFNB-1a) treatment, Daniel Pelletier, MD, reported in a poster discussion session at the annual meeting of the American Academy of Neurology.

In CARE-MS II, relapsing-remitting multiple sclerosis patients with inadequate response to prior therapy experienced improvements in MRI lesions and brain volume loss with two courses of alemtuzumab versus IFNB-1a through 2 years, and in a 4-year extension in which participants discontinued subcutaneous IFNB-1a and initiated alemtuzumab at 12 mg/day, they experienced durable efficacy in the absence of continuous treatment, explained Dr. Pelletier, a professor of neurology at the University of Southern California, Los Angeles.

In the extension, patients could receive alemtuzumab retreatment as needed for relapse/MRI activity or receive other disease-modifying therapies at the investigator’s discretion. Patients completing the extension could enter the 5-year TOPAZ study for further evaluation, he said.

Of 119 patients who completed TOPAZ year 1, and thus had 5 years of follow-up after initiating alemtuzumab, 78% were free of new, gadolinium-enhancing lesions in IFNB-1a year 2; this increased significantly to 92% in post-alemtuzumab year 2, and remained high at 85%-89% in years 3-5. Additionally, 48% of patients were free of new/enlarging T2 lesions in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2 and remained high in years 3-5.

Further, 47% of the TOPAZ patients were MRI disease activity–free in IFNB-1a year 2; this increased significantly to 81% in post-alemtuzumab year 2, and remained high at 67%-72% in years 3-5.

[email protected]

SOURCE: Pelletier D et al. Neurology. 2018 Apr 10. 90(15 Suppl.):P5.031.

LOS ANGELES – Researchers reported favorable results for the dietary supplement sulforaphane in a small, ongoing trial of children with autism.

Sulforaphane is a compound in cruciferous vegetables, especially 3-day-old broccoli sprouts. It’s sold widely online and in stores, often as broccoli sprout extract, for anticancer and other effects.

The idea of using it for autism came about after investigators noticed that, in the lab, it induced some of the cellular changes associated with fever, including upregulation of heat shock proteins, according to Kanwaljit Singh, MD, a pediatrics instructor at the University of Massachusetts, Worcester.

Fever has been reported to improve autism symptoms. So, several years ago, “we decided to do a pilot study with sulforaphane” to see if it had a similar effect, Dr. Singh said at the annual meeting of the American Academy of Neurology.

At 18 weeks, 29 young autistic men randomized to the supplement outperformed 15 randomized to placebo on the Aberrant Behavior Checklist and other measures. It was the first study of sulforaphane for autism, and it got a good deal of press attention when it was published in 2014; Dr. Singh was the lead author (Proc Natl Acad Sci U S A. 2014 Oct 28;111[43]:15550-5).

“Because we had a very good signal in our pilot study, we decided to do a slightly larger, slightly more complex clinical trial, which is ongoing right now,” he said. The results aren’t due until the second half of 2018, but he gave an interim report at the meeting.

There are 50 children with autism in the new study, aged 3-12 years. Half are randomized to sulforaphane, half to placebo, for the first 15 weeks, then all are switched to open-label sulforaphane for 15 weeks more, followed by a 6-week washout period.

The most common side effects are insomnia (28%), vomiting (19%), flatulence (17%), diarrhea (15%), and constipation (13%). A few patients have dropped out because of insomnia and diarrhea; more have dropped out because they simply didn’t want to take the pills – 125 mg of broccoli seed powder three to eight times a day, depending on weight.

[email protected]

SOURCE: Zimmerman A et al. Neurology. 2018 Apr 22; 90(15 Suppl.):N1.002.

LOS ANGELES – Researchers reported favorable results for the dietary supplement sulforaphane in a small, ongoing trial of children with autism.

Sulforaphane is a compound in cruciferous vegetables, especially 3-day-old broccoli sprouts. It’s sold widely online and in stores, often as broccoli sprout extract, for anticancer and other effects.

The idea of using it for autism came about after investigators noticed that, in the lab, it induced some of the cellular changes associated with fever, including upregulation of heat shock proteins, according to Kanwaljit Singh, MD, a pediatrics instructor at the University of Massachusetts, Worcester.

Fever has been reported to improve autism symptoms. So, several years ago, “we decided to do a pilot study with sulforaphane” to see if it had a similar effect, Dr. Singh said at the annual meeting of the American Academy of Neurology.

At 18 weeks, 29 young autistic men randomized to the supplement outperformed 15 randomized to placebo on the Aberrant Behavior Checklist and other measures. It was the first study of sulforaphane for autism, and it got a good deal of press attention when it was published in 2014; Dr. Singh was the lead author (Proc Natl Acad Sci U S A. 2014 Oct 28;111[43]:15550-5).

“Because we had a very good signal in our pilot study, we decided to do a slightly larger, slightly more complex clinical trial, which is ongoing right now,” he said. The results aren’t due until the second half of 2018, but he gave an interim report at the meeting.

There are 50 children with autism in the new study, aged 3-12 years. Half are randomized to sulforaphane, half to placebo, for the first 15 weeks, then all are switched to open-label sulforaphane for 15 weeks more, followed by a 6-week washout period.

The most common side effects are insomnia (28%), vomiting (19%), flatulence (17%), diarrhea (15%), and constipation (13%). A few patients have dropped out because of insomnia and diarrhea; more have dropped out because they simply didn’t want to take the pills – 125 mg of broccoli seed powder three to eight times a day, depending on weight.

[email protected]

SOURCE: Zimmerman A et al. Neurology. 2018 Apr 22; 90(15 Suppl.):N1.002.

LOS ANGELES – Researchers reported favorable results for the dietary supplement sulforaphane in a small, ongoing trial of children with autism.

Sulforaphane is a compound in cruciferous vegetables, especially 3-day-old broccoli sprouts. It’s sold widely online and in stores, often as broccoli sprout extract, for anticancer and other effects.

The idea of using it for autism came about after investigators noticed that, in the lab, it induced some of the cellular changes associated with fever, including upregulation of heat shock proteins, according to Kanwaljit Singh, MD, a pediatrics instructor at the University of Massachusetts, Worcester.

Fever has been reported to improve autism symptoms. So, several years ago, “we decided to do a pilot study with sulforaphane” to see if it had a similar effect, Dr. Singh said at the annual meeting of the American Academy of Neurology.

At 18 weeks, 29 young autistic men randomized to the supplement outperformed 15 randomized to placebo on the Aberrant Behavior Checklist and other measures. It was the first study of sulforaphane for autism, and it got a good deal of press attention when it was published in 2014; Dr. Singh was the lead author (Proc Natl Acad Sci U S A. 2014 Oct 28;111[43]:15550-5).

“Because we had a very good signal in our pilot study, we decided to do a slightly larger, slightly more complex clinical trial, which is ongoing right now,” he said. The results aren’t due until the second half of 2018, but he gave an interim report at the meeting.

There are 50 children with autism in the new study, aged 3-12 years. Half are randomized to sulforaphane, half to placebo, for the first 15 weeks, then all are switched to open-label sulforaphane for 15 weeks more, followed by a 6-week washout period.

The most common side effects are insomnia (28%), vomiting (19%), flatulence (17%), diarrhea (15%), and constipation (13%). A few patients have dropped out because of insomnia and diarrhea; more have dropped out because they simply didn’t want to take the pills – 125 mg of broccoli seed powder three to eight times a day, depending on weight.

[email protected]

SOURCE: Zimmerman A et al. Neurology. 2018 Apr 22; 90(15 Suppl.):N1.002.

LOS ANGELES – No new safety signals have emerged in multiple sclerosis patients treated with ocrelizumab, according to ongoing follow-up and postmarketing surveillance.

As of September 2017, patients with relapsing or primary progressive MS who were part of the pivotal OPERA I and II and ORATORIO trials – including phases 2 and 3 and open-label extensions – as well as an all-exposure population that included patients from prior studies, had nearly 9,500 patient-years of exposure to ocrelizumab (Ocrevus), a humanized anti-CD20 monoclonal antibody. The all-exposure population contributed about 1,500 of those patient-years, Stephen Hauser, MD, reported at the annual meeting of the American Academy of Neurology.

solitude72/iStockphoto

Trial participants received 600-mg doses intravenously every 24 weeks in all three trials; in OPERA I/II, they received 96 weeks of treatment with the first dose given as two 300-mg infusions split by 14 days, and, in ORATORIO, they received at least 120 weeks of treatment with all doses split, Dr. Hauser said.

In the phase 2 study, they received split doses of 600-mg or 2,000-mg infusions through week 24; then through week 96, they received either 600-mg or 1,000-mg doses; those receiving 600 mg included those who started at that dose and those who received placebo or interferon beta-1a 30 mcg, and those receiving 1,000 mg were those who started on ocrelizumab at 2,000 mg.

The comparators were placebo in the ORATORIO and phase 2 trials, and interferon beta-1a given at a dose of 44 mcg subcutaneously three times weekly (OPERA I and II) or 30 mcg intramuscularly each week in the phase 2 trial.

All patients were offered enrollment into open-label extension studies, and “there was rather massive interest in joining the open-label extension and continuing open-label extension in both trials,” he said.

“And earlier here at the AAN [meeting] we presented the clinical efficacy data from the open-label extension, now 2 years completed – so 4 years from onset of the study – in patients who received ocrelizumab continuously for [relapsing-remitting] MS during that time period, or who switched from three-times-weekly interferon beta-1a to ocrelizumab ... and the data continue to show the positive outcomes reported in the original trials,” he added.

Further, follow-up data on MRI outcomes from the open-label extensions demonstrate that the effects on focal disease activity and on progression persists and is durable with ongoing treatment, he noted.

“In conclusion, there is no pattern of serious infections or malignancies that has emerged thus far with increased exposure, but obviously long-term follow-up and postmarketing requirement studies are needed to monitor long-term patient safety and rare events that couldn’t be captured here,” he said.

This study was sponsored by F. Hoffmann-La Roche. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Symbiotix, Annexon Biosciences, Bionure, Molecular Stethoscope, and for serving on the Board of Directors of Neurona Therapeutics.

[email protected]

SOURCE: Hauser S et al. Neurology. 2018 Apr 9;(15 Suppl.):S36.001.

LOS ANGELES – No new safety signals have emerged in multiple sclerosis patients treated with ocrelizumab, according to ongoing follow-up and postmarketing surveillance.

As of September 2017, patients with relapsing or primary progressive MS who were part of the pivotal OPERA I and II and ORATORIO trials – including phases 2 and 3 and open-label extensions – as well as an all-exposure population that included patients from prior studies, had nearly 9,500 patient-years of exposure to ocrelizumab (Ocrevus), a humanized anti-CD20 monoclonal antibody. The all-exposure population contributed about 1,500 of those patient-years, Stephen Hauser, MD, reported at the annual meeting of the American Academy of Neurology.

solitude72/iStockphoto

Trial participants received 600-mg doses intravenously every 24 weeks in all three trials; in OPERA I/II, they received 96 weeks of treatment with the first dose given as two 300-mg infusions split by 14 days, and, in ORATORIO, they received at least 120 weeks of treatment with all doses split, Dr. Hauser said.

In the phase 2 study, they received split doses of 600-mg or 2,000-mg infusions through week 24; then through week 96, they received either 600-mg or 1,000-mg doses; those receiving 600 mg included those who started at that dose and those who received placebo or interferon beta-1a 30 mcg, and those receiving 1,000 mg were those who started on ocrelizumab at 2,000 mg.

The comparators were placebo in the ORATORIO and phase 2 trials, and interferon beta-1a given at a dose of 44 mcg subcutaneously three times weekly (OPERA I and II) or 30 mcg intramuscularly each week in the phase 2 trial.

All patients were offered enrollment into open-label extension studies, and “there was rather massive interest in joining the open-label extension and continuing open-label extension in both trials,” he said.

“And earlier here at the AAN [meeting] we presented the clinical efficacy data from the open-label extension, now 2 years completed – so 4 years from onset of the study – in patients who received ocrelizumab continuously for [relapsing-remitting] MS during that time period, or who switched from three-times-weekly interferon beta-1a to ocrelizumab ... and the data continue to show the positive outcomes reported in the original trials,” he added.

Further, follow-up data on MRI outcomes from the open-label extensions demonstrate that the effects on focal disease activity and on progression persists and is durable with ongoing treatment, he noted.

“In conclusion, there is no pattern of serious infections or malignancies that has emerged thus far with increased exposure, but obviously long-term follow-up and postmarketing requirement studies are needed to monitor long-term patient safety and rare events that couldn’t be captured here,” he said.

This study was sponsored by F. Hoffmann-La Roche. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Symbiotix, Annexon Biosciences, Bionure, Molecular Stethoscope, and for serving on the Board of Directors of Neurona Therapeutics.

[email protected]

SOURCE: Hauser S et al. Neurology. 2018 Apr 9;(15 Suppl.):S36.001.

LOS ANGELES – No new safety signals have emerged in multiple sclerosis patients treated with ocrelizumab, according to ongoing follow-up and postmarketing surveillance.

As of September 2017, patients with relapsing or primary progressive MS who were part of the pivotal OPERA I and II and ORATORIO trials – including phases 2 and 3 and open-label extensions – as well as an all-exposure population that included patients from prior studies, had nearly 9,500 patient-years of exposure to ocrelizumab (Ocrevus), a humanized anti-CD20 monoclonal antibody. The all-exposure population contributed about 1,500 of those patient-years, Stephen Hauser, MD, reported at the annual meeting of the American Academy of Neurology.

solitude72/iStockphoto

Trial participants received 600-mg doses intravenously every 24 weeks in all three trials; in OPERA I/II, they received 96 weeks of treatment with the first dose given as two 300-mg infusions split by 14 days, and, in ORATORIO, they received at least 120 weeks of treatment with all doses split, Dr. Hauser said.

In the phase 2 study, they received split doses of 600-mg or 2,000-mg infusions through week 24; then through week 96, they received either 600-mg or 1,000-mg doses; those receiving 600 mg included those who started at that dose and those who received placebo or interferon beta-1a 30 mcg, and those receiving 1,000 mg were those who started on ocrelizumab at 2,000 mg.

The comparators were placebo in the ORATORIO and phase 2 trials, and interferon beta-1a given at a dose of 44 mcg subcutaneously three times weekly (OPERA I and II) or 30 mcg intramuscularly each week in the phase 2 trial.

All patients were offered enrollment into open-label extension studies, and “there was rather massive interest in joining the open-label extension and continuing open-label extension in both trials,” he said.

“And earlier here at the AAN [meeting] we presented the clinical efficacy data from the open-label extension, now 2 years completed – so 4 years from onset of the study – in patients who received ocrelizumab continuously for [relapsing-remitting] MS during that time period, or who switched from three-times-weekly interferon beta-1a to ocrelizumab ... and the data continue to show the positive outcomes reported in the original trials,” he added.

Further, follow-up data on MRI outcomes from the open-label extensions demonstrate that the effects on focal disease activity and on progression persists and is durable with ongoing treatment, he noted.

“In conclusion, there is no pattern of serious infections or malignancies that has emerged thus far with increased exposure, but obviously long-term follow-up and postmarketing requirement studies are needed to monitor long-term patient safety and rare events that couldn’t be captured here,” he said.

This study was sponsored by F. Hoffmann-La Roche. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Symbiotix, Annexon Biosciences, Bionure, Molecular Stethoscope, and for serving on the Board of Directors of Neurona Therapeutics.

[email protected]

SOURCE: Hauser S et al. Neurology. 2018 Apr 9;(15 Suppl.):S36.001.

LOS ANGELES – There’s substantially higher risk of relapse and epilepsy after acute disseminated encephalomyelitis when children present with serum antibodies against myelin oligodendrocyte glycoprotein, according to British investigators.

“Traditionally, we told parents that ADEM [acute disseminated encephalomyelitis] is typically monophasic. I do tell parents now that the risk of relapse is higher if we see” myelin oligodendrocyte glycoprotein antibodies (MOG-Ab), said senior investigator Yael Hacohen, MBBS, DPhil, a pediatric neurology lecturer at University College London.

There was also a strong trend for relapsing disease when children presented with seizures, and an increased risk of post-ADEM epilepsy with oligoclonal bands on cerebrospinal fluid analysis, a marker of inflammation.

ADEM is an acute CNS demyelinating disorder primarily affecting young children, often after upper respiratory tract infections and occasionally after measles, mumps, and rubella vaccination. Signs can include limb weakness, stumbling, and coma. Many children recover without incident, but some don’t.

There’s been an increasing number of reports of children – and adults – presenting with antibodies against MOG, a glycoprotein on the outermost layer of the myelin sheath. Its exact function is unknown, but antibodies have been found in a number of inflammatory CNS conditions, and its role in pathogenesis is being explored. Testing is available for clinical use, but it isn’t standardized. For now, titer levels aren’t being used to guide treatment at University College London, Dr. Hacohen said at the American Academy of Neurology annual meeting.

M. Alexander Otto/MDedge News

[email protected]

SOURCE: Rossor T et al. Neurology. 2018 Apr 90(15 Suppl.):S35.004.

LOS ANGELES – There’s substantially higher risk of relapse and epilepsy after acute disseminated encephalomyelitis when children present with serum antibodies against myelin oligodendrocyte glycoprotein, according to British investigators.

“Traditionally, we told parents that ADEM [acute disseminated encephalomyelitis] is typically monophasic. I do tell parents now that the risk of relapse is higher if we see” myelin oligodendrocyte glycoprotein antibodies (MOG-Ab), said senior investigator Yael Hacohen, MBBS, DPhil, a pediatric neurology lecturer at University College London.

There was also a strong trend for relapsing disease when children presented with seizures, and an increased risk of post-ADEM epilepsy with oligoclonal bands on cerebrospinal fluid analysis, a marker of inflammation.

ADEM is an acute CNS demyelinating disorder primarily affecting young children, often after upper respiratory tract infections and occasionally after measles, mumps, and rubella vaccination. Signs can include limb weakness, stumbling, and coma. Many children recover without incident, but some don’t.

There’s been an increasing number of reports of children – and adults – presenting with antibodies against MOG, a glycoprotein on the outermost layer of the myelin sheath. Its exact function is unknown, but antibodies have been found in a number of inflammatory CNS conditions, and its role in pathogenesis is being explored. Testing is available for clinical use, but it isn’t standardized. For now, titer levels aren’t being used to guide treatment at University College London, Dr. Hacohen said at the American Academy of Neurology annual meeting.

M. Alexander Otto/MDedge News

[email protected]

SOURCE: Rossor T et al. Neurology. 2018 Apr 90(15 Suppl.):S35.004.

LOS ANGELES – There’s substantially higher risk of relapse and epilepsy after acute disseminated encephalomyelitis when children present with serum antibodies against myelin oligodendrocyte glycoprotein, according to British investigators.

“Traditionally, we told parents that ADEM [acute disseminated encephalomyelitis] is typically monophasic. I do tell parents now that the risk of relapse is higher if we see” myelin oligodendrocyte glycoprotein antibodies (MOG-Ab), said senior investigator Yael Hacohen, MBBS, DPhil, a pediatric neurology lecturer at University College London.

There was also a strong trend for relapsing disease when children presented with seizures, and an increased risk of post-ADEM epilepsy with oligoclonal bands on cerebrospinal fluid analysis, a marker of inflammation.

ADEM is an acute CNS demyelinating disorder primarily affecting young children, often after upper respiratory tract infections and occasionally after measles, mumps, and rubella vaccination. Signs can include limb weakness, stumbling, and coma. Many children recover without incident, but some don’t.

There’s been an increasing number of reports of children – and adults – presenting with antibodies against MOG, a glycoprotein on the outermost layer of the myelin sheath. Its exact function is unknown, but antibodies have been found in a number of inflammatory CNS conditions, and its role in pathogenesis is being explored. Testing is available for clinical use, but it isn’t standardized. For now, titer levels aren’t being used to guide treatment at University College London, Dr. Hacohen said at the American Academy of Neurology annual meeting.

M. Alexander Otto/MDedge News

[email protected]

SOURCE: Rossor T et al. Neurology. 2018 Apr 90(15 Suppl.):S35.004.

LOS ANGELES – Someday soon, physicians will probably have solid, evidence-based guidelines on how to use mTOR inhibitors in infants with tuberous sclerosis complex.

They couldn’t come soon enough. Everolimus (Afinitor) is being used off label more and more often in children under 2 years old for seizures and other manifestations of the genetic disorder, often with a decent response.

M. Alexander Otto/MDedge News

Thirty-five children (78%) had an adverse event (AE), usually infections or lipid problems. Most were mild or moderate and didn’t affect treatment. Seven children (16%) had severe grade 3 events.

“The frequency of these AEs and the severity and type were not different from the earlier trials,” but almost 40% of the children discontinued treatment due to AEs, which was “much higher” than in past trials. “I think this represents the lack of real data with which to guide clinical judgment. There was a high tendency with any AE for discontinuation,” Dr. Krueger said.

There were more boys than girls among the 45 children. The majority were from the United States, and predominantly Cincinnati Children’s Hospital. Most had TSC2 mutations, which are associated with worse disease than TSC1 mutations.

Dr. Krueger reported research funding and personal compensation from Novartis, maker of everolimus. Almost all of his coinvestigators reported ties to the company. The work was supported by the Tuberous Sclerosis Alliance, which is funded in part by Novartis.

[email protected]

SOURCE: Krueger D et al. Neurology. 2018 Apr 90(15 Suppl.):S35.003.

LOS ANGELES – Someday soon, physicians will probably have solid, evidence-based guidelines on how to use mTOR inhibitors in infants with tuberous sclerosis complex.

They couldn’t come soon enough. Everolimus (Afinitor) is being used off label more and more often in children under 2 years old for seizures and other manifestations of the genetic disorder, often with a decent response.

M. Alexander Otto/MDedge News

Thirty-five children (78%) had an adverse event (AE), usually infections or lipid problems. Most were mild or moderate and didn’t affect treatment. Seven children (16%) had severe grade 3 events.

“The frequency of these AEs and the severity and type were not different from the earlier trials,” but almost 40% of the children discontinued treatment due to AEs, which was “much higher” than in past trials. “I think this represents the lack of real data with which to guide clinical judgment. There was a high tendency with any AE for discontinuation,” Dr. Krueger said.

There were more boys than girls among the 45 children. The majority were from the United States, and predominantly Cincinnati Children’s Hospital. Most had TSC2 mutations, which are associated with worse disease than TSC1 mutations.

Dr. Krueger reported research funding and personal compensation from Novartis, maker of everolimus. Almost all of his coinvestigators reported ties to the company. The work was supported by the Tuberous Sclerosis Alliance, which is funded in part by Novartis.

[email protected]

SOURCE: Krueger D et al. Neurology. 2018 Apr 90(15 Suppl.):S35.003.

LOS ANGELES – Someday soon, physicians will probably have solid, evidence-based guidelines on how to use mTOR inhibitors in infants with tuberous sclerosis complex.

They couldn’t come soon enough. Everolimus (Afinitor) is being used off label more and more often in children under 2 years old for seizures and other manifestations of the genetic disorder, often with a decent response.

M. Alexander Otto/MDedge News

Thirty-five children (78%) had an adverse event (AE), usually infections or lipid problems. Most were mild or moderate and didn’t affect treatment. Seven children (16%) had severe grade 3 events.

“The frequency of these AEs and the severity and type were not different from the earlier trials,” but almost 40% of the children discontinued treatment due to AEs, which was “much higher” than in past trials. “I think this represents the lack of real data with which to guide clinical judgment. There was a high tendency with any AE for discontinuation,” Dr. Krueger said.

There were more boys than girls among the 45 children. The majority were from the United States, and predominantly Cincinnati Children’s Hospital. Most had TSC2 mutations, which are associated with worse disease than TSC1 mutations.

Dr. Krueger reported research funding and personal compensation from Novartis, maker of everolimus. Almost all of his coinvestigators reported ties to the company. The work was supported by the Tuberous Sclerosis Alliance, which is funded in part by Novartis.

[email protected]

SOURCE: Krueger D et al. Neurology. 2018 Apr 90(15 Suppl.):S35.003.

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

[email protected]

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

[email protected]

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008

LOS ANGELES – Parkinson’s disease patients with long-standing disease should be screened for glucose dysregulation and treated with insulin releasing drugs, instead of insulin sensitizers, when necessary, according to a French investigation that compared 50 patients with 50 healthy controls matched for age, sex, and body mass index.

The subjects underwent a 75-g oral glucose tolerance test. Glucose levels were higher in the Parkinson’s disease (PD) group from about 60 minutes through the end of the test at 180 minutes; the differences were statistically significant at 90 and 150 minutes. The total blood glucose area under the time curve (AUC) was significantly higher in the PD group (1,187 vs. 1,101 mmol.min l-1; P = .05).

[email protected]

SOURCE: Marques A et al. Neurology. 2018 Apr 90(15 Suppl.):S3.008