Acquired Demyelinating Syndromes Research Articles

Diagnostic Value of Oligoclonal Bands in Children: A Nationwide Population-Based Cohort Study

ObjectiveWe evaluated the diagnostic value of cerebrospinal fluid oligoclonal bands in individuals less than 18 years of age. MethodsIn a nationwide population-based setting, we retrieved data on 2055 children's oligoclonal band examination, including concordant cerebrospinal fluid biomarkers, during 1994 to 2017. Case ascertainment was by review of medical records and diagnostic codes. We used Fisher's exact test to explore distribution differences of oligoclonal band positivity in acquired demyelinating syndromes (ADS) before and after age 12 years and calculated the sensitivity, specificity, positive predictive value, and negative predictive value of oligoclonal bands to distinguish ADS from the other diagnostic groups. ResultsMedian age at oligoclonal band examination was 15.2 years (range = 1.8 to 18.0), and 10% had presence of cerebrospinal fluid oligoclonal bands. Oligoclonal band positivity was the highest in ADS (52%), but it was age dependent: 21% in children with ADS before age 12 years and 68% in children aged 12 through 17 years (P < 0.0001) owing to the higher incidence of multiple sclerosis in the latter. Cerebrospinal fluid oligoclonal bands were not predictive of ADS before age 12 years compared with the other diagnostic groups. However, cerebrospinal fluid oligoclonal bands in children aged 12 through 17 years were highly predictive of ADS compared with central nervous system infections and non–ADS immune-mediated central nervous system diseases (positive predictive value: 0.89; 95% confidence interval = 0.82 to 0.94; P < 0.0001), but negative oligoclonal bands were not discriminatory (negative predictive value: P = 0.17). ConclusionsIn a clinical setting, cerebrospinal fluid oligoclonal band examination may be of higher yield in children aged 12 through 17 years if there is clinical suspicion of multiple sclerosis, and in such circumstances a positive test supports a diagnosis of multiple sclerosis.

Real-world validation of the 2017 McDonald criteria for pediatric MS.

ObjectiveTo compare the diagnostic accuracy of the McDonald 2017 vs the McDonald 2010 criteria to predict a second attack of MS (clinically definite MS [CDMS]) at the first attack of acquired demyelinating syndromes (ADS).MethodsOne hundred sixty-four children (aged <18 years) with an incident attack of ADS were included in a prospective multicenter study between June 2006 and December 2016. Brain (and spinal if available) MRI was performed ≤3 months after symptom onset. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were compared at baseline between the 2010 and 2017 criteria.ResultsAmong the 164 patients, 110 patients (67%) presented without encephalopathy (ADS–, female 63%; median age 14.8 years, IQR 11.3–16.1years) and 54 (33%) with encephalopathy (acute disseminated encephalomyelitis [ADEM], female 52%; median age 4.0 years, IQR 2.6–6.1 years). Of the 110 ADS– patients, 52 (47%) were diagnosed with CDMS within a median follow-up of 4.5 years (IQR 2.6–6.7 years). The sensitivity was higher for the 2017 criteria than for the 2010 criteria (83%; 95% CI 67–92, vs 49%; 95% CI 33–65; p < 0.001), but the specificity was lower (73%; 95% CI 59–84 vs 87%; 95% CI 74–94, p = 0.02). At baseline, 48 patients fulfilled the 2017 criteria compared with 27 patients when using the 2010 criteria. The results for children aged <12 years without encephalopathy were similar. In patients with ADEM, 8% fulfilled the 2010 criteria and 10% the 2017 criteria at baseline but no patient fulfilled the criteria for CDMS.ConclusionsThe McDonald 2017 criteria are more sensitive than the McDonald 2010 criteria for predicting CDMS at baseline. These criteria can also be applied in children aged <12 years without encephalopathy but not in children with ADEM.Classification of evidenceThis study provides Class II evidence that in children with ADS, the 2017 McDonald criteria are more sensitive but less specific than the 2010 McDonald criteria for predicting CDMS.

MRI findings in pediatric neuromyelitis optica spectrum disorder with MOG antibody: Four cases and review of the literature

BackgroundMyelin oligodendrocyte glycoprotein antibodies (MOG Abs) are frequently detected in pediatric acquired demyelinating syndrome (ADS), and MOG-Ab-positive ADS differs from multiple sclerosis (MS) and aquaporin-4 (AQP4)-Ab-positive neuromyelitis optica spectrum disorder (NMOSD) in terms of age distribution, therapeutic response, and prognosis. MethodsBased on medical records, we retrospectively evaluated patients with MOG-Ab-positive NMOSD treated in the acute phase who were followed up in the chronic phase at our hospital from January 2011 to December 2017. ResultsThe patients comprised two boys and two girls aged 3–12 (median, 8) years. Peak MOG-Ab titers were 1:2048 to 1:32768 (median, 1:10240), and the relapse rate ranged from 0 to 1.25 times/year (median, 0.59 times/year); no sequelae were observed in any cases. Lesions other than those of optic neuritis were distributed at the cortex in one patient, subcortical white matter in four, deep white matter in three, and brainstem in one, all of which were disseminated lesions. No lesions were found in the corpus callosum, periventricular white matter, diencephalon, and regions adjacent to the third and fourth ventricles. The lesions tended to be asymptomatic, and two patients aged >5 years had well-demarcated lesions. ConclusionAll the patients showed disseminated lesions in the subcortical region to deep white matter, which were different from those found in MS and AQP4-Ab-positive NMOSD and were consistent with the characteristics of brain lesions in MOG-Ab-positive ADS, including other disease types.

Physical activity and dentate gyrus volume in pediatric acquired demyelinating syndromes.

ObjectiveTo assess the association between daily moderate-to-vigorous physical activity (MVPA) and dentate gyrus volume (DGv) in pediatric patients with acquired demyelinating syndromes (ADSs) of the CNS.MethodsCross-sectional analysis of accelerometry (7 days) and research protocol MRI data from 12 pediatric MS and 18 children with monophasic ADS (monoADS). Total brain and DGv were quantified using standardized methods. The association of daily minutes of MVPA with normalized DGv (nDGv) was assessed using multivariable generalized linear models.ResultsMedian (interquartile range) MVPA was lower in MS patients [9.5 (14)] and exhibited less variation than in monoADS patients [24.5 (47)]. nDGv did not differ significantly between groups [mean nDGv (SD) [cm3]: MS 0.34 (0.1); monoADS 0.4 (0.1); p = 0.100]. In the monoADS group, every 1-minute increase in MVPA was associated with a 2.4-mm3 increase in nDGv (p = 0.0017), an association that was independent of age at incident demyelination, time from incident demyelination, sex, and brain white matter T2 lesion volume. No significant association was found between MVPA and nDGv (−2.6 mm3/min, p = 0.16) in the MS group.ConclusionsHigher MVPA associates with greater nDGv in children who have recovered from monophasic demyelination. Larger studies are required to determine whether MVPA can promote regional brain development, or limit tissue damage, in youth with MS.

Pediatric-onset multiple sclerosis is associated with reduced parental health–related quality of life and family functioning

Background: Diagnosis of multiple sclerosis (MS) during childhood has the potential to impact the affected child’s self-perception and the health-related quality of life (HRQoL) of the family. Objective: To evaluate the impact of chronic disease, in children ascertained as having MS and their families, when compared to those with monophasic acquired demyelinating syndrome (monoADS). Methods: In a national prospective cohort study of pediatric acquired demyelinating syndromes (ADS), the HRQoL of children and their families was captured using the Pediatric Quality of Life Inventory (PedsQL™) Modules. Results: Participants (58 MS; 178 monoADS) provided cross-sectional HRQoL data a median (interquartile range (IQR)) of 4.1 (2.0–6.0) years after disease onset. The HRQoL of parents of children with MS and their family functioning was lower when compared to that of parents and families of children with monoADS (both p < 0.001); parents of children with MS reported greater emotional dysfunction, worry, worse communication, and lower family functioning irrespective of clinical disease activity. Self-reports of the MS and monoADS participants did not suggest a difference in overall HRQoL or fatigue after adjusting for age of the child at the time of assessment. Conclusion: While children with MS did not self-report lower HRQoL compared to children who experienced monoADS, the diagnosis of MS during childhood was negatively associated with parental HRQoL and family functioning.

T-cell activation marker sCD27 is associated with clinically definite multiple sclerosis in childhood-acquired demyelinating syndromes

Background: Cerebrospinal fluid (CSF) levels of T-cell activation marker soluble CD27 (sCD27) are associated with subsequent disease activity after a first attack of suspected MS in adults. The predictive value for disease course in children with acquired demyelinating syndromes (ADS) is unknown. Objectives: To assess the predictive value of sCD27 levels for clinically definite multiple sclerosis (CDMS) diagnosis in childhood ADS. Methods: Children <18 years with a first demyelinating event were prospectively included and followed. Soluble CD27 was determined in CSF using an enzyme-linked immunosorbent assay (ELISA). Cox regression analyses were used to calculate hazard ratios (HRs) for CDMS. Results: A total of 94 ADS children were included (ADS with encephalopathy (ADS+) n = 33 and ADS without encephalopathy (ADS–) n = 61). Of the 61 ADS– children, 21 (48%) were diagnosed with CDMS during follow-up. At baseline, sCD27 levels were higher in patients with a future CDMS diagnosis (n = 29) than in monophasic ADS+ (n = 30), monophasic ADS– (n = 28) and relapsing non-MS patients (n = 7; p < 0.001). In ADS– patients, sCD27 was associated with CDMS (HR = 1.8 per 100 U/mL increase in sCD27 levels, p = 0.031), after adjustments for age, oligoclonal bands and the presence of dissemination in space on baseline magnetic resonance imaging (MRI). Conclusion: CSF sCD27 levels at first attack of demyelination were associated with CDMS diagnosis in children. This makes sCD27 a potential clinically relevant quantitative marker when performing routine CSF diagnostics.

Pediatric acquired demyelinating syndromes: a nationwide validation study of the Danish National Patient Register.

ObjectiveTo validate the Danish National Patient Register’s (NPR) diagnoses of pediatric acquired demyelinating syndromes (ADS) including multiple sclerosis (MS).Study design and settingWe identified ADS diagnostic groups using International Classification of Diseases (ICD) codes and reviewed medical records to validate the NPR diagnoses during 2008–2015.ResultsAmong 409 children in the study, 184 children had a validated and final ADS diagnosis after reviewing medical records as follows: optic neuritis (ON; n=46), transverse myelitis (TM; n=16), acute disseminated encephalomyelitis (ADEM; n=50), clinically isolated syndrome (CIS) including dissemination in space (CIS [DIS]) but not dissemination in time (n=6), neuromyelitis optica spectrum disorder (NMOsd; n=5), and MS (n=61). During the mean follow-up of 4.6 years, 33% of children initially diagnosed with monophasic ADS progressed to MS. Positive predictive value (PPV) was 0.71 (95% confidence interval [CI] =0.62–0.80) for ON, 0.64 (95% CI =0.43–0.82) for TM, 0.93 (95% CI =0.84–0.98) for MS, 0.27 (95% CI =0.19–0.35) for CIS, 0.43 (95% CI =0.10–0.82) for NMOsd, and 0.15 (95% CI =0.10–0.20) for ADEM. Assuming complete coverage for non-MS ADS, the sensitivity was 0.99 (95% CI =0.93–1.00) for ON, 0.83 (95% CI =0.36–1.00) for CIS (DIS), and 0.80 (95% CI =0.56–0.94) for TM, but only 0.58 (95% CI =0.43–0.72) for ADEM and 0.60 (95% CI =0.15–0.95) for NMOsd.ConclusionPPV was high for MS and considered acceptable for ON and TM; therefore, these ICD revision 10 (ICD-10) codes from the NPR are useful for epidemiological studies. Conversely, PPV was low for CIS and ADEM; NMOsd was inconclusive.

Acute tansverse myelitis in children

Acute transverse myelitis (ATM) is a rare inflammatory and demyelinating disorder of spinal cord with an immune – mediated basis (1). It is potentially a devastating disorder with variable outcomes that can present with subacute onset of motor, sensory and autonomic dysfunction.(2) TM can occur as an isolated condition, usually as a postinfectious disorder or may be the first presentation of relapsing acquired demyelinating syndromes (ADS) that include acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), and neuromyelitis optica (NMO). ATM also, must be distinguished from compressive and noninflamatory myelopathies. Diagnostic evaluation, prognosis, recurrence risk, and treatment plans are different among these entities

Myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies are highly specific in children with acquired demyelinating syndromes.

Our objectives were to evaluate the utility of measuring myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies (Ab) in clinical practice and describe their associated neurological phenotypes in children. Between 2012 and 2017, 371 children with suspected acquired demyelinating syndromes (ADS) seen in three tertiary centres were tested for MOG-Ab and AQP4-Ab. Medical notes were retrospectively reviewed, and clinical and demographic data compiled. Clinical phenotyping was performed blinded to the antibody results. After review, 237 of the 371 were diagnosed with ADS. Of these, 76 out of 237 (32.1%) were MOG-Ab positive and 14 out of 237 (5.9%) were AQP4-Ab positive. None were positive for both autoantibodies. All 134 patients with non-ADS were negative for MOG-Ab. MOG-Ab were identified in 45 out of 70 (64.3%) patients presenting with acute disseminated encephalomyelitis (ADEM) and in 24 out of 25 patients with relapsing ADEM. Thirty-six out of 75 (48%) MOG-Ab positive patients relapsed. Of the 33 children with neuromyelitis optic spectrum disorder, 14 were AQP4-Ab positive, 13 were MOG-Ab positive, and 6 were seronegative. Of the children with longitudinal samples, 8 out of 13 AQP4-Ab remained positive during the disease course compared to 35 out of 43 MOG-Ab (13/16 monophasic and 22/27 relapsing). Myelin oligodendrocyte glycoprotein antibodies were identified in a third of children with ADS. Almost half of the MOG-Ab positive children relapsed and the majority of them remained antibody positive over 4-years follow-up. Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are highly specific for acquired demyelinating syndromes (ADS). Myelin oligodendrocyte glycoprotein antibodies are not identified in children with peripheral demyelination or genetic leukodystrophies/hypomyelination. Up to 48% of MOG-Ab ADS paediatric patients relapse, higher than previously thought. Seroconversion to MOG-Ab negative status is infrequent; patients may test MOG-Ab positive at follow-up sampling even when asymptomatic. Myelin oligodendrocyte glycoprotein antibodies status should only be used in conjunction with the clinical information to guide maintenance therapy.

MRI of the first event in pediatric acquired demyelinating syndromes with antibodies to myelin oligodendrocyte glycoprotein

Antibodies against the myelin oligodendrocyte glycoprotein (MOG-Ab) can be detected in various pediatric acquired demyelinating syndromes (ADS). Here, we analyze the spectrum of neuroradiologic findings in children with MOG-Ab and a first demyelinating event. The cerebral and spinal MRI of 69 children with different ADS was assessed in regard to the distribution and characteristics of lesions. Children with acute disseminated encephalomyelitis (n=36) or neuromyelitis optica spectrum disorder (n=5) presented an imaging pattern characterized predominantly by poorly demarcated lesions with a wide supra- and infratentorial distribution. Younger children also tended to have poorly defined and widespread lesions. The majority of patients with an isolated optic neuritis (n=16) only presented small non-specific brain lesions or none at all. A longitudinally extensive transverse myelitis mainly affecting the cervical, and less often so the thoracic, lumbar, and conus regions, was detected in 31 children. The three children of our cohort who were then finally diagnosed with multiple sclerosis had at onset already demarcated white matter lesions as well as transverse myelitis. In conclusion, children with MOG seropositive ADS present disparate, yet characteristic imaging patterns. These patterns have been seen to correlate to the disease entity as well as to age of symptom onset.

The contribution of secondhand tobacco smoke exposure to pediatric multiple sclerosis risk

Background: Pediatric acquired demyelinating syndromes (ADSs) are monophasic (mono-ADS) in 70% of cases and represent the first attack of multiple sclerosis (MS) in 30%. Secondhand tobacco smoke (SHS) exposure has been implicated as a risk factor for adult-onset MS. Little is known about whether SHS presents an additive risk beyond genetic factors and other environmental exposures associated with pediatric MS. Methods: This study examined SHS exposure in 216 children with mono-ADS and 81 children with MS. Interactions between SHS, HLA-DRB1*15 alleles, serum 25-hydroxyvitamin D concentrations, and serological evidence of remote Epstein–Barr virus (EBV) exposure were evaluated. Results: SHS exposure was more common in children with MS (37% exposed) compared to mono-ADS (29.5% exposed). Compared to mono-ADS, SHS exposure was not an independent risk factor for MS. When both SHS exposure and HLA-DRB1*15 were present, the odds for MS increased (odds ratio (OR) = 3.7; 95% confidence interval (CI): 1.17–11.9) compared to mono-ADS. Interactions between SHS and vitamin D or EBV did not associate with MS. Conclusion: Exposure to SHS is a risk factor for central nervous system (CNS) demyelination. Results suggest that SHS exposure and HLA-DRB1*15 interact to increase risk for MS in children diagnosed with mono-ADS.

Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome.

To assess the prognostic value of MOG antibodies (abs) in the differential diagnosis of acquired demyelinating syndromes (ADS). Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands (OCB) in children with ADS and 24 months of follow-up were reviewed in this observational prospective multicenter hospital-based study. Two hundred ten children with ADS were included and diagnosed with acute disseminated encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD) (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis (MS) (n = 37) after the first episode. MOG-abs were predominantly found in ADEM (57%) and less frequently in NMOSD (25%), CIS (25%), or MS (8%). Increased MOG-ab titers were associated with younger age (p = 0.0001), diagnosis of ADEM (p = 0.005), increased CSF cell counts (p = 0.011), and negative OCB (p = 0.012). At 24-month follow-up, 96 children had no further relapses. Thirty-five children developed recurrent non-MS episodes (63% MOG-, 17% AQP4-abs at onset). Seventy-nine children developed MS (4% MOG-abs at onset). Recurrent non-MS episodes were associated with high MOG-ab titers (p = 0.0003) and older age at onset (p = 0.024). MS was predicted by MS-like MRI (p < 0.0001) and OCB (p = 0.007). An MOG-ab cutoff titer ≥1:1,280 predicted a non-MS course with a sensitivity of 47% and a specificity of 100% and a recurrent non-MS course with a sensitivity of 46% and a specificity of 86%. Our results show that the presence of MOG-abs strongly depends on the age at disease onset and that high MOG-ab titers were associated with a recurrent non-MS disease course.

Pediatric-onset multiple sclerosis and other acquired demyelinating syndromes of the central nervous system in Denmark during 1977–2015: A nationwide population-based incidence study

Background: The incidence of acquired demyelinating syndromes (ADS) including multiple sclerosis (MS) has never been investigated in a Danish pediatric population. Objectives: We estimated the nationwide age- and sex-specific incidence of pediatric ADS including MS. Methods: Data were sourced from the Danish Multiple Sclerosis Registry, providing cases of pediatric MS for 1977–2015, and the National Patient Register, providing cases of ADS during 2008–2015. All medical records were reviewed to validate the register-based diagnoses. Results: We identified 364 cases of pediatric MS occurring during 1977–2015 (incidence rate = 0.79 per 100,000 person-years). MS was exceptionally rare before puberty, but the incidence rose considerably from 9 years in girls and 11 years in boys. The female-to-male ratio was 2.5; the median age at onset was 16 years (range = 7–17 years). The MS incidence rate was relatively stable through the study period. During 2008–2015, we identified 219 ADS cases. The incidence was 2.29 per 100,000 person-years with considerable differences in the age peaks for the separate ADS. Conclusion: The incidence rates of MS and other ADS in Denmark were higher than those reported for some other European countries. Referral bias and classification differences may account for this disparity, in particular the age-intervals and the definition of onset.

Clinical features in very early-onset demyelinating disease with anti-MOG antibody

BackgroundThe clinical features of patients with very early-onset acquired demyelinating syndrome (ADS) with the anti-myelin oligodendrocyte glycoprotein (MOG) antibody are unknown. We investigated the clinical characteristics and described detailed treatment of weekly intramuscular interferon β-1a (IFNβ-1a) in children aged <4years with ADS and the anti-MOG antibody. MethodsWe conducted a retrospective chart review of patients with anti-MOG positivity who were diagnosed as having multiple sclerosis (MS) at <4years of age. ResultsSubjects comprised 2 boys and 2 girls. Initial symptoms included ataxia, facial paresis, status epilepticus, and encephalopathy. Abnormal lesions on magnetic resonance imaging scans were often detected in the brainstem and cerebellum as well as the cerebrum. All patients started receiving IFNβ-1a at age 3.1–3.5years. The initial doses ranged from 3 to 6μg, which were 1/10–1/5 doses, respectively, for adults. During 0.6–4.3years of IFNβ-1a administration, all patients had flu-like symptoms, and 1 patient had an increased liver enzyme level. Although 1 patient discontinued IFNβ-1a therapy because of frequent relapses, no patient discontinued therapy due to severe adverse events. ConclusionsThis case series adds novel information regarding the clinical features of children <4years old with ADS and the anti-MOG antibody.

MOG Spectrum Diseases

In the past, MOG antibodies have been thought to be associated with the pathological events leading to MS. Several studies in large cohorts found only rarely children who were finally diagnosed with MS as having MOG antibodies at initial presentation, pleading strongly against a MS diagnosis in children with acquired demyelinating syndromes (ADS) and positive MOG antibodies. On the other hand, serum MOG antibodies have been detected in several recurrent non-MS demyelinating inflammatory diseases such as ADEM followed by optic neuritis (ADEMON), AQP4-Ab-negative neuromyelitis spectrum disorders (NMOSD), recurrent optic neuritis and more recently in children with multiphasic disseminated encephalomyelitis (MDEM). This presentation will summarize important clinical and neuroradiological aspects of children with ADS and MOG antibodies.

Monophasic demyelination reduces brain growth in children.

To investigate how monophasic acquired demyelinating syndromes (ADS) affect age-expected brain growth over time. We analyzed 83 pediatric patients imaged serially from initial demyelinating attack: 18 with acute disseminated encephalomyelitis (ADEM) and 65 with other monophasic ADS presentations (monoADS). We further subdivided the monoADS group by the presence (n = 33; monoADSlesion) or absence (n = 32; monoADSnolesion) of T2 lesions involving the brain at onset. We used normative data to compare brain volumes and calculate age- and sex-specific z scores, and used mixed-effect models to investigate their relationship with time from demyelinating illness. Children with monophasic demyelination (ADEM, non-ADEM with brain lesions, and those without brain involvement) demonstrated reduced age-expected brain growth on serial images, driven by reduced age-expected white matter growth. Cortical gray matter volumes were not reduced at onset but demonstrated reduced age-expected growth afterwards in all groups. Brain volumes differed from age- and sex-expected values to the greatest extent in children with ADEM. All patient groups failed to recover age-expected brain growth trajectories. Brain volume, and more importantly age-expected brain growth, is negatively affected by acquired demyelination, even in the absence of chronicity, implicating factors other than active inflammation as operative in this process.

A nationwide survey of pediatric acquired demyelinating syndromes in Japan.

Objective:To investigate the clinical and epidemiologic features of pediatric acquired demyelinating syndromes (ADS) of the CNS in Japan.Methods:We conducted a nationwide survey and collected clinical data on children with ADS aged 15 years or younger, who visited hospitals between 2005 and 2007.Results:Among 977 hospitals enrolled, 723 (74.0%) responded to our inquiries and reported a total of 439 patients as follows: 244 with acute disseminated encephalomyelitis (ADEM), 117 with multiple sclerosis (MS), 14 with neuromyelitis optica (NMO), and 64 with other ADS. We collected and analyzed detailed data from 204 cases, including those with ADEM (66), MS (58), and NMO (10). We observed the following: (1) the estimated annual incidence rate of pediatric ADEM in Japan was 0.40 per 100,000 children (95% confidence interval [CI], 0.34–0.46), with the lowest prevalence in the north; (2) the estimated prevalence rate of MS was 0.69 per 100,000 children (95% CI, 0.58–0.80), with the lowest prevalence in the south; (3) NMO in Japan was rare, with an estimated prevalence of 0.06 per 100,000 children (95% CI, 0.04–0.08); and (4) the sex ratio and mean age at onset varied by ADS type, and (5) male/female ratios correlated with ages at onset in each ADS group.Conclusions:Our results clarify the characteristic clinical features of pediatric ADS in the Japanese population.

Evolution of MRI abnormalities in paediatric acute disseminated encephalomyelitis.

Acute disseminating encephalomyelitis (ADEM) is an inflammatory demyelinating disease affecting the central nervous system and mainly occurs in young children. Children who initially presented with ADEM can be diagnosed with multiple sclerosis (MS) in case new non-encephalopathic clinical symptoms occur with new lesions on MRI at least three months after onset of ADEM. We aim to study the timing of MRI abnormalities related to the evolution of clinical symptoms in our Dutch paediatric ADEM cohort. The Dutch database for acquired demyelinating syndromes (ADS) was screened for children under age eighteen fulfilling the international consensus diagnostic criteria for ADEM. Children were eligible when the first MRI was performed within the first three months after onset of clinical symptoms and at least one brain follow-up MRI was available for evaluation. Forty-two children with ADEM were included (median age four years two months). All available MRIs and medical records were assessed and categorised as 'improved', 'deteriorated' and 'unchanged'. We found that during clinical recovery, new lesions and enlargement of existing MRI lesions occurred in the first three months in about 50% of the performed MRIs. In contrast, this was rarely seen more than three months after first onset of ADEM. We recommend to perform a brain MRI as a reference scan three months after onset. Follow-up imaging should be compared with this scan in order to prevent an incorrect diagnosis of MS after ADEM.

Pediatric acquired CNS demyelinating syndromes: Features associated with multiple sclerosis.

Approximately one-third of children with an acquired demyelinating syndrome (ADS) will be diagnosed with multiple sclerosis (MS), either at onset according to the 2010 McDonald criteria, or on the basis of clinical or MRI evidence of relapsing disease, in the majority of patients within 2-4 years. ADS in adolescents, female patients, and patients with polyfocal deficits is associated with the highest likelihood of MS, while children with acute disseminated encephalomyelitis, those with documented preceding infection, and ADS presentation in young children more commonly portends a monophasic outcome. While pediatric MS associates with similar genetic risk alleles as have been documented in adult-onset MS, such associations are not diagnostically valuable at the individual level. The presence of antibodies directed against aquaporin-4 strongly supports a diagnosis of neuromyelitis optica, and should be assayed in children manifesting with severe optic neuritis, longitudinally extensive myelitis, or brainstem/hypothalamic syndromes. Further research will determine whether other antibody signatures are indicative of relapsing demyelination distinct from MS.

Pediatric transverse myelitis.

Pediatric acute transverse myelitis (ATM) is an immune-mediated CNS disorder and contributes to 20% of children experiencing a first acquired demyelinating syndrome (ADS). ATM must be differentiated from other presentations of myelopathy and may be the first presentation of relapsing ADS such as neuromyelitis optica (NMO) or multiple sclerosis (MS). The tenets of the diagnostic criteria for ATM established by the Transverse Myelitis Consortium Working Group can generally be applied in children; however, a clear sensory level may not be evident in some. MRI lesions are often centrally located with high T2 signal intensity involving gray and neighboring white matter. Longitudinally extensive ATM occurs in the majority. Asymptomatic lesions on brain MRI are seen in more than one-third and predict MS or NMO. The role of antibodies such as myelin oligodendrocyte glycoprotein in monophasic and relapsing ATM and their significance in therapeutic approaches remain unclear. ATM is a potentially devastating condition with variable outcome and presents significant cumulative demands on health and social care resources. Children generally have a better outcome than adults, with one-half making a complete recovery by 2 years. There is need for standardization of clinical assessment and investigation protocols to enable international collaborative studies to delineate prognostic factors for disability and relapse. There are no robust controlled trials in children or adults to inform optimal treatment of ATM, with one study currently open to recruitment. This review provides an overview of current knowledge of clinical features, investigative workup, pathogenesis, and management of ATM and suggests future directions.