S. Lori

Cognitive and psychosocial features of childhood and juvenile MS

Objective: To assess the impact of multiple sclerosis (MS) on cognitive and psychosocial functioning in childhood and juvenile cases. Methods: We used an extensive neuropsychological battery assessing IQ, memory, attention/concentration, executive functions, and language. Fatigue and depression were also measured. An interview on school and daily living activities was obtained from the parents. Performance of cases was compared with that of demographically matched healthy controls. Results: Sixty-three patients and 57 healthy controls were assessed. Five patients (8%) exhibited a particularly low IQ (<70). Criteria for cognitive impairment (failure on at least three tests) were fulfilled in 19 patients (31%), whereas 32 patients (53%) failed at least two tests. Beyond deficits in memory, complex attention, and executive functions, the profile of deficits was characterized by involvement of linguistic abilities. In the regression analysis, the only significant predictor of cognitive impairment was an IQ score lower than 90 (odds ratio [OR] 18.2, 95% CI 4.6–71.7, p < 0.001). Considering the IQ score as a dependent variable, the only significant predictor was represented by younger age at onset (OR 0.7, 95% CI 0.5–0.9, p = 0.009). Depressive symptoms were reported by 6% of the cases, and fatigue was reported by 73% of the cases. MS negatively affected school and everyday activities in 56% of the subjects. Conclusions: In childhood and juvenile cases, multiple sclerosis (MS) is associated with cognitive impairment and low IQ scores, the latter related to younger age at onset. These aspects are of critical importance in helping children and adolescents with MS to manage their difficulties and psychosocial challenges.

Cognitive and psychosocial features in childhood and juvenile MS Two-year follow-up

Objective: To assess the evolution of cognitive and psychosocial functioning in a cohort of childhood and juvenile multiple sclerosis (MS) cases after a mean period of 2 years had elapsed since baseline evaluation. Methods: In this cohort study, we used the same extensive neuropsychological battery with alternative versions of the tests assessing memory, attention/concentration, executive functions, and language. Fatigue and depression were also measured. An interview on school and daily living activities was obtained from the parents. The cognitive performance of the patients was compared with that of demographically matched healthy controls (HC). Results: Fifty-six patients and 50 HC were assessed. At follow-up, criteria for cognitive impairment (failure on at least 3 tests) were fulfilled in 39 patients (70%) and 75% of the cases were classified as having a deteriorating cognitive performance. Changes were prominent in tests of verbal memory, complex attention, verbal fluency, and receptive language. In the regression analysis, the only significant predictor of cognitive deterioration was older age of the subject (odds ratio 1.9, 95% confidence interval 1.2–2.9, p = 0.003). Psychiatric disorders, most frequently depression, were diagnosed in 12 patients (30.5%). Fatigue was reported by 21% of the patients. MS negatively affected school and everyday activities in 30% to 40% of the subjects. Conclusions: Our findings confirm the importance of systematic assessment of cognitive and psychosocial issues in children and teens with MS. The progressive nature of the cognitive difficulties emphasizes the need for developing effective treatment strategies.

Fatigue and its relationships with cognitive functioning and depression in paediatric multiple sclerosis

Background: There is limited information on fatigue and its clinical and psychosocial correlates in children and adolescents with multiple sclerosis (MS). Objective: To assess the relationships between fatigue, cognitive functioning and depression in paediatric MS. Methods: The study cohort consisted of patients with MS recruited for an Italian collaborative study on cognitive and psychosocial functioning in paediatric MS. The present assessment included evaluation of fatigue on the Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale, cognitive functioning on an extensive neuropsychological battery and depression on the Children’s Depression Inventory (CDI). A psychiatric interview through the Kiddie-SADS-Present and Lifetime Version was also administered. Results: In total, 57 patients with relapsing–remitting MS were compared with 70 healthy controls. Percentages of fatigued patients ranged from 9% to 14% according to self-reports, and from 23% to 39% according to parent reports. Fatigue was significantly related with higher scores on the CDI (p < 0.03). Higher levels of self-reported cognitive fatigue were associated with impaired performance on a problem-solving test, whereas higher levels of parent-reported cognitive fatigue were associated with impairment on tests of verbal learning, processing speed, complex attention and verbal comprehension. Conclusions: Our data show that fatigue can affect a sizeable proportion of paediatric MS patients, and confirm the association between fatigue and depressive symptoms in MS. They also highlight the difficulties of fatigue assessment in the paediatric population and provide a few clues to further research in the field.

Neuropsychological features in childhood and juvenile multiple sclerosis Five-year follow-up

Objective: The aim of the study was to perform a third cognitive assessment in our pediatric-onset multiple sclerosis (MS) patient cohort and determine predictors of the individual cognitive outcome. Methods: After 4.7 ± 0.7 years from baseline evaluation, 48 of 63 patients in the original cohort were reassessed on an extensive neuropsychological battery and compared with 46 healthy controls. Two alternate versions of the tests were used at different assessment points. Cognitive impairment was defined as the failure of ≥3 tests; individual change in the cognitive impairment index was measured. Results: At year 5, 38% of the subjects with MS fulfilled our criterion for impairment. Between years 2 and 5, regarding individual cognitive impairment index change, 66.7% of the patients improved. However, comparing baseline and 5-year testing (when the same versions of the tests were used), cognitive impairment index deterioration was observed in 56% of the patients, improvement in 25%, and stability in 18.8%. A deteriorating performance was related to male sex, younger age and age at MS onset, and lower education. None of these variables, however, was retained in the multivariate analysis. Conclusions: Cognitive outcome in pediatric-onset MS can be heterogeneous. Progression of cognitive problems in a few subjects and potential for compensation and improvement in others call for systematic cognitive screening in this population and development of effective treatment strategies.

The brief neuropsychological battery for children: a screening tool for cognitive impairment in childhood and juvenile multiple sclerosis

Background A critical problem with neuropsychological assessment in children and adolescents with multiple sclerosis (MS) is the absence of a standardized, well-validated neuropsychological battery specifically tailored for detecting disease-related cognitive problems in this age range. Objective To develop a Brief Neuropsychological Battery for Children (BNBC) with MS. Methods We assessed cognitive functions in 61 patients with childhood and juvenile MS and 58 demographically matched healthy controls through an extensive neuropsychological battery. Results In MS patients, we found a proportion of cognitive impairment of 41%. In the BNBC, we included the tests with higher discriminating ability (the Selective Reminding Test, the Symbol Digit Modalities Test, the Trail Making Test, and the Vocabulary test from the Wechsler Intelligence Scale for children). The BNBC yielded a sensitivity of 96% and a specificity of 76%. Conclusion Our findings provide preliminary evidence of the usefulness of the BNBC as a screening tool for detecting cognitive impairment in childhood and juvenile MS cases.

Psychosocial issue in children and adolescents with multiple sclerosis

In adult-onset multiple sclerosis (MS) cases, major depression, fatigue and psychological distress are common, whereas there is little information on these issues in children with the disease. The aim of this study was to assess psychosocial disorders in an Italian cohort of children and adolescent with MS. We evaluated 56 patients through self-assessment scales of depression (Children Depression Inventory) and fatigue (Fatigue Severity Scale), a psychiatric interview [Kiddie-SADS-Present and Lifetime Version (K-SADS-PL)] and an interview on school and everyday activities. Significant fatigue was found in 11 patients (20%). Twelve of the 39 patients who underwent the K-SADS-PL received a formal diagnosis of an affective disorder. Moreover, MS affected school activities in 28% of cases, daily living activities in 41% and social relationships in 28%. Our study confirms the critical role of psychosocial difficulties in children and adolescents with MS and provides a few cues to clinical management.

Prognostic value of somatosensory evoked potentials in comatose children: a systematic literature review

PurposeTo review the predictive powers of SEPs in comatose children after acute brain injury.MethodsMEDLINE, EMBASE, OVID, ISI Web of Knowledge, BIOMED Central and the Cochrane Library (1981–2007) were searched. First, predictive values were calculated for each primary study. Second, we analysed effects of different factors on the SEP diagnostic odds ratio by meta-regression. Third, we compared SEP predictive values in children and in adults.ResultsWe selected 14 studies covering 732 patients; analysis was conducted in 11, while the other 3 were used for simple qualitative examination. In individual papers, the presence of SEP predicted favourable outcomes as shown by the area under both sROC curves being 0.958. The same value was shown by SEP absence for predicting unfavourable outcomes. All covariates showed no significant effects on diagnostic accuracy, but only a slight non-significant trend. For SEP grading, a simple sub-group analysis showed a high predictive value for non-awakening for absence of SEPs (PPV 97.0%) and a high prognostic power to predict awakening for normal SEPs (PPV 92.2%). Pathological SEPs did not show reliable predictivity. In children, the presence of SEPs showed a high prognostic power similar to that in adults.ConclusionThis study supports the use of SEPs in the integrated process of outcome prediction after acute brain injury in children. Caution is recommended in predicting unfavourable outcomes in patients with an absence of SEPs in both TBI and HIE comas. Future studies are needed to resolve the issue of the effect of aetiology and age on SEPs predictive power.

No association between chronic cerebrospinal venous insufficiency and pediatric-onset multiple sclerosis

Objective: Chronic cerebrospinal venous insufficiency (CCSVI) was hypothesized to play a causative role in multiple sclerosis (MS). The assessment of pediatric-onset MS (POMS) may provide a unique window of opportunity to study hypothesized risk factors in close temporal association with the onset of the disease. Methods: Internal jugular veins, vertebral veins and intracranial veins were evaluated with extracranial and intracranial ultrasound in 15 POMS and 16 healthy controls. Assessor’s blinding was maintained during the study. We considered subjects positive to CCSVI when at least two criteria were fulfilled. Results: CCSVI frequency was comparable between POMS and controls (p > 0.05). Clinical features were not significantly different between CCSVI-positive and CCSVI-negative patients. Conclusions: Our findings add to previous data pointing against a causative role of CCSVI in MS.

The cognitive reserve theory in the setting of pediatric-onset multiple sclerosis.

Background: The study of cognitive reserve (CR) in relationship with cognitive impairment (CI) in pediatric-onset multiple sclerosis (POMS) may provide cues to identifying subjects at higher risk of impairment and scope for therapeutic strategies. Objectives: To assess the potential impact of CR on cognition in a cohort of POMS patients. Methods: In all, 48 POMS patients were followed up for 4.7 ± 0.4 years. CI was defined as the failure of ⩾3 tests on an extensive neuropsychological battery. Change of neuropsychological performance was assessed through the Reliable Change Index (RCI) method. At baseline, CR was estimated by measuring the intelligence quotient (IQ). The relationships were assessed through multivariable regression analyses. Results: At baseline, CI was detected in 14/48 (29.2%) patients. Two out of 57 healthy control (HC; 3.5%) met the same criteria of CI (p < 0.001). A deteriorating cognitive performance using the RCI method was observed in 18/48 patients (37.6%). Among the 34 cases who were cognitively preserved at baseline, a higher reserve predicted stable/improving performance (odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.03–1.20; p = 0.006). Conclusion: Our results suggest that higher CR in POMS patients may protect from CI, particularly in subjects with initial cognitive preservation, providing relevant implications for counseling and rehabilitation strategies.

IgG and IgM antibodies to the refolded MOG1–125 extracellular domain in humans

Antibodies to MOG in serum have a dubious prognostic value in multiple sclerosis. The MOG recombinant protein conformational properties relevant to the antigenic activity are unknown. We employed a solid-phase ELISA based on a product (rMOG(ED)(His)(6)) expressed in E. coli after subcloning the cDNA of the extracellular domain of rat MOG, performing a refolding procedure on column and affinity purification. The far-UV Circular Dichroism (CD) spectra of rMOG(ED)(His)(6) showed a β-sheet, a characteristic feature of the Ig-fold. However, in MS sera and controls we failed to detected IgM or IgG antibodies.