Early Immunotherapy and Longer Corticosteroid Treatment Are Associated With Lower Risk of Relapsing Disease Course in Pediatric MOGAD

Background and Objectives We sought to identify early factors associated with relapse and outcome in paediatric-onset myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Methods In a multicenter retrospective cohort of pediatric MOGAD (≤18 years), onset features and treatment were compared in patients with monophasic vs relapsing disease (including cases with follow-up ≥12 months after onset or relapse at any time) and in patients with final Expanded Disability Status Scale (EDSS) 0 vs ≥1 at last follow-up (including cases with followup >3 months after last event or EDSS0 at any time). Multivariable logistic regression models were used to evaluate factors associated with relapsing disease course and EDSS ≥ 1 at final follow-up. Results Seventy-five children were included (median onset age 7 years; median 30 months of follow-up). Presentation with acute disseminated encephalomyelitis was more frequent in children aged 8 years or younger (66.7%, 28/42) than in older patients (30.3%, 10/33) (p = 0.002), whereas presentation with optic neuritis was more common in children older than 8 years (57.6%, 19/33) than in younger patients (21.4%, 9/42) (p = 0.001). 40.0% (26/65) of patients relapsed. Time to first relapse was longer in children aged 8 years or younger than in older patients (median 18 vs 4 months) (p = 0.013). Factors at first event independently associated with lower risk of relapsing disease course were immunotherapy <7 days from onset (6.7-fold reduced odds of relapsing course, OR 0.15, 95% CI 0.03–0.61, p = 0.009), corticosteroid treatment for ≥5 weeks (6.7-fold reduced odds of relapse, OR 0.15, 95% CI 0.03–0.80, p = 0.026), and abnormal optic nerves on onset MRI (12.5-fold reduced odds of relapse, OR 0.08, 95% CI 0.01–0.50, p = 0.007). 21.1% (15/71) had EDSS ≥ 1 at final follow-up. Patients with a relapsing course had a higher proportion of final EDSS ≥ 1 (37.5%, 9/24) than children with monophasic disease (12.8%, 5/39) (p = 0.022, univariate analysis). Each 1-point increment in worst EDSS at onset was independently associated with 6.7-fold increased odds of final EDSS ≥ 1 (OR 6.65, 95% CI 1.33–33.26, p = 0.021). Discussion At first attack of pediatric MOGAD, early immunotherapy, longer duration of corticosteroid treatment, and abnormal optic nerves on MRI seem associated with lower risk of relapse, whereas higher disease severity is associated with greater risk of final disability (EDSS ≥ 1)

DTI-Fiber Tractography of Cerebellar Pathways can be Related to Neurocognitive Deficits in Children with Posterior Fossa Tumors

Background/Objectives: Lesions of the cerebellum fibers may result in cognitive function impairments in brain tumor survivors. A more differentiated identification of neu- roanatomical structures contributing to the extent of this damage is needed. We examined the relationship between long-term cognitive dysfunction and alteration of cerebel- lar pathways using diffusion tensor imaging (DTI) and tractography. Design/Methods: DTI-based tractography was performed in patients with posterior fossa tumors. Spinocerebellar (SC), dento-rubro-thalamo-cortical (DRTC), fronto-ponto- cerebellar (FPC), parieto-ponto-cerebellar (PPC), occipito- ponto-cerebellar (OPC) and temporo-ponto-cerebellar (TPC) tracts were analyzed concerning fractional anisotropy (FA) and volumetric measurements. Cognitive outcome was assessed with the Developmental Neuropsychological scale (NEPSY). The correlations between NEPSY scores and fiber tracts were tested with linear regression analysis. Results: Seven patients with cerebellar tumor were included (median age 63 months - IQR: 39-80). All children had com- plete surgery: 2/7 (29%) had medulloblastoma, and 5/7 (71%) pilocytic astrocytoma. Median IQ was 83.5 (74.75-83.87) and correlation was found with right SC (R2 for number of fibers 0.50; volume 0.90) and DRTC tracts (R2 for volume 0.58; FA 0.52). Patients showed worst performance in the follow- ing items: attention, correlated with right OPC (R2 for num- ber of fibers 0.53; FA -0.86) and PPC tracts (R2 of number of fibers 0.59; volume 0.61; FA 0.52); memory for design, related to left FPC tract (R2 of number for fibers 0.63; vol- ume -0.63); memory for names, correlated with right DRTC tract (R2 for number of fibers 0.85; volume 0.90); visuospa- tial function, inversely correlated with left OPC tract (R2 of number of fibers -0.81; volume -0.66); and social perception, correlated with left SC (R2 of number for fibers 0.55; volume 0.53) and right PPC tracts (R2 of number for fibers 0.90; vol- ume 0.69). Conclusions: DTI may be useful to identify relevant struc- tures of the cerebellar pathway and possibly avoid surgically induced long-term neurological sequelae

Prognostic Factors of Hydrocephalus in Children with Brain Tumors: A Retrospective Analysis

Background/Objectives: Hydrocephalus is one of the main complications of brain tumors in children, involving about 50% of cases at diagnosis. It usually resolves with surgical tumor resection but could persist up to 10-40% of cases. The aim of this study is to identify prognostic factors associated with persistent hydrocephalus in a pediatric population of patients with brain tumors. Design/Methods: Retrospective case note review of 56 newly diagnosed brain tumour patients referred between 04/2012 and 01/2018 to our regional paediatric neuro-oncology ser- vice was carried out to evaluate preoperative and postoper- ative Magnetic Resonance Imaging (MRI) and to determine Evans\u2019 Index (EI) and fronto-occipital horn ratio (FOHR) for each scan. Chi-square and Fischer test were used to analyze categorical variables as appropriate. Mann-Whitney analysis was used for the evaluation of continuous variables. A p-value 0.46 at diagnosis (p: 0.042) were related to a higher prevalence of persistent hydrocephalus and therefore to the need for a cerebrospinal fluid drain device. Conclusions: Identifying pre-operatively patients at risk for developing persistent hydrocephalus would avoid delays in the execution of interventions for the placement of perma- nent cerebrospinal fluid drain devices. This study finds that a FOHR> 0.46 at diagnosis could impact on the therapeu- tic management of children with hydrocephalus and brain tumors. Prospective and large-scale studies are needed in order to standardize this approach

Possible association between the integrity of cerebellar pathways and neurocognitive performance in children with posterior fossa tumors

Background: Cerebellar tumor survivors often exhibit neuropsychological deficits that could be related to alterations in cerebro-cerebellar networks. This is a pilot study designed to understand if diffusion tensor imaging (DTI)-based tractography is able to identify possible correlations between cerebellar white matter structure and cognitive outcome in children on long-term follow-up for posterior fossa (PF) tumors who were thoroughly assessed for neuropsychological functioning. Methods: DTI-based tractography was performed in pediatric patients with PF tumors. Fractional anisotropy (FA) and volumetric measurements of spinocerebellar, dentorubrothalamocortical and corticopontocerebellar tracts were analyzed. Cognitive and neuropsychological functioning was assessed by the Wechsler Intelligence Scale for Children\u2013IV Edition (WISC-IV) and the Developmental Neuropsychological Assessment (NEPSY II). The associations between Full-Scale Intelligence Quotient (FSIQ), NEPSY-II scores, and fiber tracts were tested by the Spearman rank correlation coefficient. Results: Seven patients (median age at diagnosis five years, range, 3-13) treated for medulloblastoma (2/7; 29%) and pilocytic astrocytoma (5/7; 71%) were retrospectively evaluated. All children had complete surgery. The median FSIQ was 84 (range, 67-93). Patients presented with several deficits on many NEPSY-II tasks; in particular, memory was impaired in nearly half of them. FSIQ and neurocognitive tasks significantly correlated with specific corticopontocerebellar tracts. Conclusion: Children on follow-up for PF tumor showed scattered cognitive impairments, including deficits in long-term and immediate memory. Tractography allowed us to describe a possible association between the integrity of cerebellar pathways and neurocognitive performance, suggesting that the myelinization of these fibers may represent an indicator for the development of long-term cognitive sequelae