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There are few tests to accurately assess the degree and effects of lupus in children, but Ped-ANAM proves to be a promising option.
Lupus patients who develop the condition in childhood have a greater chance of also experiencing neuropsychiatric problems. But, to date, there have been few tests available to accurately assess the degree and effects of this condition.
A new study, published in Arthritis Care & Research, examined both existing tests that analyze mental and cognitive impairments in children who have lupus, known as neuropsychiatric systemic lupus erythematosus (NPSLE), as well as a new pediatric version of the Automated Neuropsychological Assessment Metrics (Ped-ANAM) evaluation. The review is designed to highlight how well these tests can accurately diagnose problems, leading to effective treatment.
“[Neuropsychiatric systemic lupus erythematosus] can affect the central, peripheral, and autonomic nervous systems, resulting in headaches, strokes, psychiatric disturbance, and cognitive dysfunction,” study authors wrote. “Given the lack of specific diagnostic tests, NPSLE remains largely a diagnosis of exclusion.”
Currently, there are no blood, imaging, or immunological biomarker tests that can verify whether a patient has NPSLE, and the reasons behind it remain unclear. Providers must rely on subjective tests that look at cognition, simple and complex attention, memory, language, reasoning and problem-solving, executive functions, psychomotor speed, and visual-spatial processing.
According to existing data, patients who develop lupus in childhood – usually over age 5 – are more likely to encounter NPSLE than those with adult-onset – 30% to 95% versus 21% to 70%, respectively. And, because NPSLE can negatively impact mental development, accurate identification and treatment is key.
Published research suggests anti-phospholipid antibodies play a role in cognitive impairment and could promote micro-thrombus formation and non-inflammatory vasculopathy, leading to ischemic brain damage. Methyl-D-aspartate receptors are also associated with lupus-related cognitive problems, including learning and memory formation. Additionally, anti-ribosomal P antibodies are linked to psychosis and depression - two conditions that could be involved in cognitive decline among children with lupus.
MRI studies confirm that 81% of these children experience cerebral and cerebellar volume loss with white matter lesions present in the prefrontal and frontal regions. These are areas of active myelination during childhood and adolescence, so any damage could have long-term negative effects.
Formal neurocognitive testing is considered the gold standard for determining a child’s true cognitive functioning, the researchers said. Some are questionnaire-based methods; others are computerized neuropsychological batteries.
To better test children, the American College of Rheumatology altered its standardized cognitive test for adults with lupus. The new version assesses working memory, psychomotor speed, attention, and visuoconstructional ability. Using these tests effectively can be difficult, though, because they last for three hours, and fatigue and language proficiency can alter test outcomes.
Other test options include the Mini Mental Status Exam for children over age four, but it must be paired with other screening tools to offer an accurate assessment. School academic performance records also provide important clues into a child’s cognitive abilities. Children with NPSLE often have attention and learning difficulties.
Computerized tests, such as the Cambridge Neuropsychological Testing Automated Battery (CANTAB), offer highly-standardized measurements in real-time. Children as young as age four can take the 90-minute CANTAB, but it’s challenging and impractical because it focuses on planning, spatial working memory, executive functioning, and non-verbal memory span.
Better, more accurate testing for low cognitive functioning and risk of NPSLE in children is needed, however, investigators said. To sidestep the challenges presented by existing test options, providers and investigators developed the Pediatric Automated Neuropsychological Assessment Metrics (Ped-ANAM). It includes age-appropriate material from the Automated Neuropsychological Assessment Metrics adult version.
The test lowered the reading level, simplified test stimuli and instruction, and offered longer response times. It’s currently available in English, French, German, Spanish, Portuguese, Chinese, Hindi, and Arabic.
Ped-ANAM, which can be administered to children as young as age 9, evaluates accuracy, speed, cognitive efficiency, and consistency. Each child’s scores are compared to those provided by healthy individuals.
According to this study’s investigators, the test identifies children with lupus who also have clinically-relevant cognitive impairment with 97% accuracy. These children are at considerable risk, they said, of experiencing NPSLE symptoms.
Children can complete Ped-ANAM is roughly 20-30 minutes in a quiet, distraction-free environment with a test administrator available to answer any questions. Results from case examples reveal children with NPSLE have slower reaction times, below average spatial processing, and below average reasoning, as well as below average memory function.
Investigators suggest children complete Ped-ANAM at least twice – once for baseline and once to assess and performance change. Previous studies have found low results are associated with reduced brain volumes in children with lupus.
Overall, investigators said, monitoring a child’s cognitive ability as an ultimate indicator of brain health is critical. Long-standing neuropsychological testing is still the standard for measuring a child’s cognitive capabilities, but this strategy presents challenges with long administration times and the availability of trained administration personnel.
In the future, they said, using Ped-ANAM with children who have lupus can be an effective, convenient method for screening for and monitoring their cognitive functioning.
Brunner, Hermine, et al. “The Challenges of Diagnosing Cognitive Dysfunction with Neuropsychiatric Systemic Lupus Erythematosus in Childhood,” Dec. 19, 2016. Arthritis Care & Research. DOI: 10.1002/acr.23163.
Brey, R.L., et al. “Neuropsychiatric syndromes in lupus: prevalence using standardized definitions,” April 23, 2002. Neurology. DOI: 10.1212/WNL.58.8.1214.
Tucker, L.B., et al. “Adult- and childhood-onset systemic lupus erythematosus: a comparison of onset, clinical features, serology, and outcome,” Sept. 1995. British Journal of Rheumatology. DOI: 10.1093/rheumatology/34.9.866.
Zelko, F., et al. “Academic outcomes in childhood-onset systemic lupus erythematosus,” Aug. 2012. Arthritis Care & Research. DOI: 10.1002/acr.21681