MS-Like Syndromes Slow Pediatric Brain Growth, Cognition

SEATTLE — Children and adolescents who have an acute demyelinating syndrome or multiple sclerosis may experience lasting impairment in brain growth or cognition, according to two prospective studies.

In one study, Dr. Douglas L. Arnold and his fellow researchers found a slower-than-expected rate of brain growth over 1 year in children with a history of one acute demyelinating event.

In a second study of children and adolescents with multiple sclerosis, Christine Till, Ph.D., and her coinvestigators found total brain volume of T2 lesions on MRI was significantly associated with cognitive impairment, which occurred in about one-third of the subjects.

“These findings are important because they indicate an effect of inflammatory activity on cognitive function,” particularly on tests that depend on integrated neural networks or efficient communication across multiple brain regions, she said.

Dr. Arnold of the Montreal Neurological Institute and Hospital at McGill University, Montreal, and his associates compared brain volume changes over 1 year using T1-weighted MRI scans in 31 children with acute demyelinating syndromes (ADS) and in 31 healthy age- and gender-matched control patients from the National Institutes of Health MRI Study of Normal Brain Development (www.brain-child.org

The rate of brain growth decreased in both groups during the year and tended to level off after 10 years of age. Before 10 years of age, ADS patients did not show atrophy, but instead showed a failure of age-anticipated brain growth. The rate of brain growth was significantly lower in 13 ADS patients younger than 10 years than it was in 12 healthy control patients (0.62%/year vs. 2.26%/year), Dr. Arnold reported at the annual meeting of the American Academy of Neurology.

However, no difference was found in the rate of brain growth after 10 years of age in 18 ADS patients (0.18%/year) and 19 healthy control patients (0.06%/year).

There appears to be a “heightened vulnerability of the more immature CNS to inflammatory brain injury, despite the capacity of younger brains to adapt … [or] respond to injury of certain sorts. This inflammation seems to interrupt some critical developmental processes and result in this failure of age-anticipated growth,” he said.

The researchers are acquiring additional data to find any corresponding neuropsychological changes and to determine whether there is any spatial localization of the changes in brain growth.

Dr. Arnold and some of his coinvestigators reported receiving research support and personal compensation from companies that manufacture drugs for MS.

The study was supported by the Multiple Sclerosis Scientific Research Foundation of Canada and the Canadian Institutes of Health Research.

In the second study, Dr. Till and her colleagues looked for signs of cognitive impairment in 32 children who presented to the pediatric MS clinic at the Hospital for Sick Children, Toronto, during 2007-2008.

Prior studies in children have shown reductions in processing speed, memory, attention, and executive function, which generally occur with greater severity at a younger age of onset and with longer disease duration.

But the “association between cognitive impairment and MRI lesion load has not been investigated in children with MS,” said Dr. Till, of the department of psychology at York University, Toronto.

Of the 32 patients, 3 were excluded from the analysis because of excessive head motion during the MRI scans, and 1 patient was excluded because of a change in diagnosis. The remaining 28 patients (22 females) were a mean of 16 years old and had a mean disease duration of 4.5 years with a relapsing-remitting course. Their median Expanded Disability Status Scale Score was 1 and 23 (82%) of them were receiving disease-modifying treatment during the study.

Of the 28 children, 10 (36%) had cognitive impairment, which Dr. Till and her associates defined as scores more than 1.5 standard deviations below the mean for their age on at least 3 of the 17 different tests in the battery. Attention and processing speed were the most commonly impaired measurements. More than 20% of the children had impaired visuomotor integration on a test that required them to copy designs of increasing complexity as well as a test that assessed cognitive flexibility and working memory.

The cognitively impaired children were younger at disease onset than were cognitively normal children (9.7 years vs. 12.5 years). Children who were cognitively impaired also had experienced a longer disease duration than did those who were cognitively normal (6.1 years vs. 3.7 years). However, the differences in both comparisons did not reach statistical significance (P = .07).

Total brain T2 lesion volume was most strongly correlated with attention, processing speed, and a global cognitive composite score. But total brain T1 lesion volume did not correlate with any of the neuropsychological testing outcomes.

In multiple linear regression models, age at disease onset was the main significant predictor of verbal intelligence and processing speed, accounting for 23%-37% of the total variation in the two. The addition of total brain lesion volume to these models accounted for another 4%-11% of the total variation.

The total brain T2 lesion volume was the main significant predictor of the global cognitive composite score as well as scores on the sustained visual attention test, after controlling for covariates.

Dr. Till said she had no conflict of interest to disclose. Two of her research collaborators disclosed receiving compensation for speaking for manufacturers of drugs for MS.

SEATTLE — Children and adolescents who have an acute demyelinating syndrome or multiple sclerosis may experience lasting impairment in brain growth or cognition, according to two prospective studies.

In one study, Dr. Douglas L. Arnold and his fellow researchers found a slower-than-expected rate of brain growth over 1 year in children with a history of one acute demyelinating event.

In a second study of children and adolescents with multiple sclerosis, Christine Till, Ph.D., and her coinvestigators found total brain volume of T2 lesions on MRI was significantly associated with cognitive impairment, which occurred in about one-third of the subjects.

“These findings are important because they indicate an effect of inflammatory activity on cognitive function,” particularly on tests that depend on integrated neural networks or efficient communication across multiple brain regions, she said.

Dr. Arnold of the Montreal Neurological Institute and Hospital at McGill University, Montreal, and his associates compared brain volume changes over 1 year using T1-weighted MRI scans in 31 children with acute demyelinating syndromes (ADS) and in 31 healthy age- and gender-matched control patients from the National Institutes of Health MRI Study of Normal Brain Development (www.brain-child.org

The rate of brain growth decreased in both groups during the year and tended to level off after 10 years of age. Before 10 years of age, ADS patients did not show atrophy, but instead showed a failure of age-anticipated brain growth. The rate of brain growth was significantly lower in 13 ADS patients younger than 10 years than it was in 12 healthy control patients (0.62%/year vs. 2.26%/year), Dr. Arnold reported at the annual meeting of the American Academy of Neurology.

However, no difference was found in the rate of brain growth after 10 years of age in 18 ADS patients (0.18%/year) and 19 healthy control patients (0.06%/year).

There appears to be a “heightened vulnerability of the more immature CNS to inflammatory brain injury, despite the capacity of younger brains to adapt … [or] respond to injury of certain sorts. This inflammation seems to interrupt some critical developmental processes and result in this failure of age-anticipated growth,” he said.

The researchers are acquiring additional data to find any corresponding neuropsychological changes and to determine whether there is any spatial localization of the changes in brain growth.

Dr. Arnold and some of his coinvestigators reported receiving research support and personal compensation from companies that manufacture drugs for MS.

The study was supported by the Multiple Sclerosis Scientific Research Foundation of Canada and the Canadian Institutes of Health Research.

In the second study, Dr. Till and her colleagues looked for signs of cognitive impairment in 32 children who presented to the pediatric MS clinic at the Hospital for Sick Children, Toronto, during 2007-2008.

Prior studies in children have shown reductions in processing speed, memory, attention, and executive function, which generally occur with greater severity at a younger age of onset and with longer disease duration.

But the “association between cognitive impairment and MRI lesion load has not been investigated in children with MS,” said Dr. Till, of the department of psychology at York University, Toronto.

Of the 32 patients, 3 were excluded from the analysis because of excessive head motion during the MRI scans, and 1 patient was excluded because of a change in diagnosis. The remaining 28 patients (22 females) were a mean of 16 years old and had a mean disease duration of 4.5 years with a relapsing-remitting course. Their median Expanded Disability Status Scale Score was 1 and 23 (82%) of them were receiving disease-modifying treatment during the study.

Of the 28 children, 10 (36%) had cognitive impairment, which Dr. Till and her associates defined as scores more than 1.5 standard deviations below the mean for their age on at least 3 of the 17 different tests in the battery. Attention and processing speed were the most commonly impaired measurements. More than 20% of the children had impaired visuomotor integration on a test that required them to copy designs of increasing complexity as well as a test that assessed cognitive flexibility and working memory.

The cognitively impaired children were younger at disease onset than were cognitively normal children (9.7 years vs. 12.5 years). Children who were cognitively impaired also had experienced a longer disease duration than did those who were cognitively normal (6.1 years vs. 3.7 years). However, the differences in both comparisons did not reach statistical significance (P = .07).

Total brain T2 lesion volume was most strongly correlated with attention, processing speed, and a global cognitive composite score. But total brain T1 lesion volume did not correlate with any of the neuropsychological testing outcomes.

In multiple linear regression models, age at disease onset was the main significant predictor of verbal intelligence and processing speed, accounting for 23%-37% of the total variation in the two. The addition of total brain lesion volume to these models accounted for another 4%-11% of the total variation.

The total brain T2 lesion volume was the main significant predictor of the global cognitive composite score as well as scores on the sustained visual attention test, after controlling for covariates.

Dr. Till said she had no conflict of interest to disclose. Two of her research collaborators disclosed receiving compensation for speaking for manufacturers of drugs for MS.

SEATTLE — Children and adolescents who have an acute demyelinating syndrome or multiple sclerosis may experience lasting impairment in brain growth or cognition, according to two prospective studies.

In one study, Dr. Douglas L. Arnold and his fellow researchers found a slower-than-expected rate of brain growth over 1 year in children with a history of one acute demyelinating event.

In a second study of children and adolescents with multiple sclerosis, Christine Till, Ph.D., and her coinvestigators found total brain volume of T2 lesions on MRI was significantly associated with cognitive impairment, which occurred in about one-third of the subjects.

“These findings are important because they indicate an effect of inflammatory activity on cognitive function,” particularly on tests that depend on integrated neural networks or efficient communication across multiple brain regions, she said.

Dr. Arnold of the Montreal Neurological Institute and Hospital at McGill University, Montreal, and his associates compared brain volume changes over 1 year using T1-weighted MRI scans in 31 children with acute demyelinating syndromes (ADS) and in 31 healthy age- and gender-matched control patients from the National Institutes of Health MRI Study of Normal Brain Development (www.brain-child.org

The rate of brain growth decreased in both groups during the year and tended to level off after 10 years of age. Before 10 years of age, ADS patients did not show atrophy, but instead showed a failure of age-anticipated brain growth. The rate of brain growth was significantly lower in 13 ADS patients younger than 10 years than it was in 12 healthy control patients (0.62%/year vs. 2.26%/year), Dr. Arnold reported at the annual meeting of the American Academy of Neurology.

However, no difference was found in the rate of brain growth after 10 years of age in 18 ADS patients (0.18%/year) and 19 healthy control patients (0.06%/year).

There appears to be a “heightened vulnerability of the more immature CNS to inflammatory brain injury, despite the capacity of younger brains to adapt … [or] respond to injury of certain sorts. This inflammation seems to interrupt some critical developmental processes and result in this failure of age-anticipated growth,” he said.

The researchers are acquiring additional data to find any corresponding neuropsychological changes and to determine whether there is any spatial localization of the changes in brain growth.

Dr. Arnold and some of his coinvestigators reported receiving research support and personal compensation from companies that manufacture drugs for MS.

The study was supported by the Multiple Sclerosis Scientific Research Foundation of Canada and the Canadian Institutes of Health Research.

In the second study, Dr. Till and her colleagues looked for signs of cognitive impairment in 32 children who presented to the pediatric MS clinic at the Hospital for Sick Children, Toronto, during 2007-2008.

Prior studies in children have shown reductions in processing speed, memory, attention, and executive function, which generally occur with greater severity at a younger age of onset and with longer disease duration.

But the “association between cognitive impairment and MRI lesion load has not been investigated in children with MS,” said Dr. Till, of the department of psychology at York University, Toronto.

Of the 32 patients, 3 were excluded from the analysis because of excessive head motion during the MRI scans, and 1 patient was excluded because of a change in diagnosis. The remaining 28 patients (22 females) were a mean of 16 years old and had a mean disease duration of 4.5 years with a relapsing-remitting course. Their median Expanded Disability Status Scale Score was 1 and 23 (82%) of them were receiving disease-modifying treatment during the study.

Of the 28 children, 10 (36%) had cognitive impairment, which Dr. Till and her associates defined as scores more than 1.5 standard deviations below the mean for their age on at least 3 of the 17 different tests in the battery. Attention and processing speed were the most commonly impaired measurements. More than 20% of the children had impaired visuomotor integration on a test that required them to copy designs of increasing complexity as well as a test that assessed cognitive flexibility and working memory.

The cognitively impaired children were younger at disease onset than were cognitively normal children (9.7 years vs. 12.5 years). Children who were cognitively impaired also had experienced a longer disease duration than did those who were cognitively normal (6.1 years vs. 3.7 years). However, the differences in both comparisons did not reach statistical significance (P = .07).

Total brain T2 lesion volume was most strongly correlated with attention, processing speed, and a global cognitive composite score. But total brain T1 lesion volume did not correlate with any of the neuropsychological testing outcomes.

In multiple linear regression models, age at disease onset was the main significant predictor of verbal intelligence and processing speed, accounting for 23%-37% of the total variation in the two. The addition of total brain lesion volume to these models accounted for another 4%-11% of the total variation.

The total brain T2 lesion volume was the main significant predictor of the global cognitive composite score as well as scores on the sustained visual attention test, after controlling for covariates.

Dr. Till said she had no conflict of interest to disclose. Two of her research collaborators disclosed receiving compensation for speaking for manufacturers of drugs for MS.