Anita Belman

Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis

We sought to determine if vitamin D status, a risk factor for multiple sclerosis, is associated with the rate of subsequent clinical relapses in pediatric‐onset multiple sclerosis.

Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study

BACKGROUND The full spectrum of clinical manifestations and outcome, and the potential importance of regional or demographic features or viral triggers in paediatric multiple sclerosis (MS), has yet to be fully characterised. Our aim was to determine some of these characteristics in children with MS. METHODS 137 children with MS and 96 control participants matched by age and geographical region were recruited in a multinational study. They underwent structured clinical-demographic interviews, review of academic performance, physical examination, disability assessment (MS patients only), and standardised assays for IgG antibodies directed against Epstein-Barr virus, cytomegalovirus, parvovirus B19, varicella zoster virus, and herpes simplex virus. FINDINGS MS was relapsing-remitting at diagnosis in 136 (99%) children. The first MS attack resembled acute disseminated encephalomyelitis (ADEM) in 22 (16%) of the children, most under 10 years old (mean age 7.4 [SD 4.2] years). Children with ADEM-like presentations were significantly younger than were children with polyfocal (11.2 [4.5] years; p<0.0001) or monofocal (12.0 [3.8] years; p=0.0005) presentations. Permanent physical disability (EDSS>or=4.0) developed within 5 years in 15 (13%) of the 120 children for whom EDSS score was available. 23 (17%) had impaired academic performance, which was associated with increasing disease duration (p=0.02). Over 108 (86%) of the children with MS, irrespective of geographical residence, were seropositive for remote EBV infection, compared with only 61 (64%) of matched controls (p=0.025, adjusted for multiple comparisons). Children with MS did not differ from controls in seroprevalence of the other childhood viruses studied, nor with respect to month of birth, sibling number, sibling rank, or exposure to young siblings. INTERPRETATION Paediatric MS is a relapsing-remitting disease, with presenting features that vary by age at onset. MS in children might be associated with exposure to EBV, suggesting a possible role for EBV in MS pathobiology.

Cognitive functioning in children and adolescents with multiple sclerosis

Objective: To examine cognitive functioning in children with multiple sclerosis (MS). Methods: The authors examined the neuropsychological profile of 37 children with a diagnosis of clinically definite MS and assessed the associations between cognitive function and clinical features. Results: Of 37 children and adolescents evaluated, 35% demonstrated significant cognitive impairment. Cognitive functioning was strongly related to several clinical variables, including current Expanded Disability Status Scale, total number of relapses, and total disease length. The consequences of MS adversely affected academic functioning in over a third of the children. Conclusions: Cognitive deficits occur in children with multiple sclerosis. Comprehensive treatment planning should involve recognition that they may require academic accommodations for their education.

AIDS Calcification of the basal ganglia in infants and children

CT or postmortem examination demonstrated calcification of the basal ganglia in eight infants and children with acquired immune deficiency syndrome. Serial CT studies documented progression of both bilateral symmetric calcium densities and cerebral atrophy. Clinical features included progressive encephalopathy with dementia, and pyramidal tract signs. Postmortem examination of four children revealed variable degrees of calcific vasopathy of the basal ganglia, involving predominantly the putamen and globus pallidus.

Neurologic manifestations in children with North American Lyme disease

To delineate the spectrum of neurologic manifestations and the relative frequencies of different syndromes associated with North American Lyme disease, we describe 96 children referred for neurologic problems in the setting of Borrelia burgdorferi infection. The most frequent neurologic symptom was headache, and the most common sign was facial palsy. Less common manifestations were sleep disturbance, and papilledema associated with increased intracranial pressure. Signs and symptoms of peripheral nervous system involvement were infrequent. The most common clinical syndromes were mild encephalopathy, lymphocytic meningitis, and cranial neuropathy (facial nerve palsy). In contrast with adult patients with neurologic Lyme disease, meningoradiculitis (Bannwarths syndrome) and peripheral neuropathy syndromes were rare. However, a “pseudotumor cerebri-like” syndrome seems to be unique to North American pediatric Lyme disease.

DEVELOPMENTAL ABNORMALITIES IN INFANTS AND CHILDREN WITH ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) AND AIDS‐RELATED COMPLEX

Children with acquired immune deficiency syndrome (AIDS) display two types of clinical picture: (1) a fullblown AIDS characterized by the presence of opportunistic infections and/or Kaposis sarcoma and (2) a prodromal stage now identified as AIDS‐related complex (ARC). Neurological complications have been identified in infants and children with the disease. This paper discusses the developmental abnormalities in 16 pediatric patients, seven with AIDS and nine with ARC, ranging in age from six months to six years. In all cases, the mothers of these children either had ARC, AIDS and/or used intravenous drugs. Developmental histories showed delayed acquisition of milestones in most children following the diagnosis of AIDS or ARC, with delayed motor milestones consistently noted in both groups. Several children with AIDS actually lost milestones as their illness progressed; this has not occurred in the ARC group. Psychometric testing revealed more severe cognitive dysfunction in the group with AIDS. Involvement of the central nervous system was documented clinically, radiologically, and/or electrophysiologically in all patients with AIDS. In the ARC group the course of the illness has shown greater variability. Medical and social factors that may contribute to the developmental abnormalities are discussed.

Common viruses associated with lower pediatric multiple sclerosis risk

Background: Because common viruses are encountered during childhood, pediatric multiple sclerosis (MS) offers a unique opportunity to investigate the influence of these viruses on disease susceptibility and the interactions between seroprevalence and select HLA genotypes. We studied seroprevalence for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV) type 1 and HLA-DRB1*1501/1503 status as predictors of pediatric MS. Methods: This was a retrospective analysis of prospectively collected demographic, clinical, and biologic data in subjects up to 18 years of age with early MS, control subjects seen at the same regional referral pediatric MS clinics, and additional healthy pediatric control subjects. Results: Patients with early pediatric MS (n = 189) and pediatric control subjects (n = 66) were tested. Epstein-Barr nuclear antigen-1 seropositivity was associated with an increased odds of MS (odds ratio [OR] 3.78, 95% confidence interval [CI] 1.52–9.38, p = 0.004) in analyses adjusted for age, sex, race, ethnicity, and HLA-DRB1*1501/1503 status. In multivariate analyses including EBV status, a remote infection with CMV (OR 0.27, 95% CI 0.11–0.67, p = 0.004) was associated with a lower risk of developing MS. Although a remote infection with HSV-1 was not associated with an increased odds of MS, a strong interaction was found between HSV-1 status and HLA-DRB1 in predicting MS (p < 0.001). HSV-1 was associated with an increased risk of MS in those without a DRB1*15 allele (OR 4.11, 95% CI 1.17–14.37, p = 0.03), whereas the effect was reversed in those who were DRB1*15-positive (OR 0.07, 95% CI 0.02–0.32, p = 0.001). Conclusions: These findings suggest that some infections with common viruses may in fact lower MS susceptibility. If this is confirmed, the pathways for risk modification remain to be elucidated.

Acquired Immunodeficiency Syndrome and the Child's Central Nervous System

Human immunodeficiency virus-1 (HIV-1) associated central nervous system disease may complicate the course of HIV-1 infection in infants and children. Neurologic dysfunction in these young patients adds significantly to the morbidity of the disease and is often a devastating complication. It is apparent that HIV-1 infection in infants and young children is complicated by numerous developmental parameters. The developmental stage of the nervous and immune systems when exposed to the virus is likely to interact in complex ways with HIV-1 variables. In order to care for these children and to design rational approaches for treatment and prevention, it is now critical to develop a better understanding of how HIV-1 affects the developing nervous system.

Cognitive Impairment Occurs in Children and Adolescents With Multiple Sclerosis Results From a United States Network

In the largest sample studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n = 187) as well as those with clinically isolated syndrome (n = 44). Participants were consecutively enrolled from six United States Pediatric Multiple Sclerosis Centers of Excellence. Participants had a mean of 14.8 ± 2.6 years of age and an average disease duration of 1.9 ± 2.2 years. A total of 65 (35%) children with multiple sclerosis and 8 (18%) with clinically isolated syndrome met criteria for cognitive impairment. The most frequent areas involved were fine motor coordination (54%), visuomotor integration (50%), and speeded information processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care.

Younger children with MS have a distinct CSF inflammatory profile at disease onset.

Background: The clinical and MRI presentation differs between earlier- and later-onset pediatric multiple sclerosis (MS), whereas the effect of age on the CSF inflammatory profile is unknown and may contribute to delayed diagnosis. Objectives: To compare the CSF cellular and immunoglobulin G (IgG) profiles between earlier- and later-onset pediatric MS. Methods: We queried the databases of 6 pediatric MS centers for earlier-onset (onset <11 years) and later-onset (≥11 and <18 years) patients with MS or clinically isolated syndrome who underwent CSF analysis within the first 3 months of presentation (observational study). We compared CSF white blood cell (WBC) differential count, IgG index, and IgG oligoclonal bands between age groups. Results: We identified 40 earlier-onset (mean age at onset = 7.2 ± 2.7 years, 60% females) and 67 later-onset pediatric MS patients (15.1 ± 1.7 years, 63% females). Although WBC count tended to be higher in earlier-onset patients (median = 9/mm3 [0–343] vs 6 [0–140], p = 0.15), they had a lower proportion of lymphocytes (70% [0–100] vs 93% [0–100] of WBCs, p = 0.0085; difference = +3% per 1-year increase of age, p = 0.0011) and higher proportion of neutrophils than later-onset patients (0.5% [0–75] vs 0% [0–50] of WBCs, p = 0.16; difference = −1% per 1-year increase of age, p = 0.033). In earlier-onset disease, fewer patients had an elevated IgG index than in the later-onset group (35% vs 68% of patients, p = 0.031). Conclusion: Age modifies the CSF profile at pediatric multiple sclerosis (MS) onset, which may mislead the diagnosis. Our findings suggest an activation of the innate rather than the adaptive immune system in the earlier stages of MS or an immature immune response.