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 follow-up >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).

A multimodal approach to the study of children treated for posterior fossa tumor: A review of the literature and a pilot study.

OBJECTIVE: The aims of the present study were: (1) to review the literature on long-lasting cognitive sequelae in children treated for Posterior Fossa Tumor and (2) to investigate anatomic functional relations in a case series of 7 children treated for PFT using magnetic resonance imaging (MRI) post-processing methods. METHODS: We retrospectively analyzed MRIs of children who underwent complete surgical resection of PFT and performed extensive neuropsychological evaluation. Tumor, ventricular volumes, and VPS insertion site were drawn on T1 volumetric MRI scans and normalized to a pediatric template. Children showed worse performances on tasks tapping executive functions, memory, visuo-motor precision, and expressive language. RESULTS: Volumes of interest related to these functions showed a maximum overlap on the left vermis and the lateral ventricle enlargement, except for impaired narrative fluency -which was associated with left lateral ventricle enlargement- and narrative memory -which was related to the right vermis and the enlarged fourth ventricle. CONCLUSION: Results suggest that anatomic functional relations in children treated for PFT are related to a combination of different pathophysiological factors.

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-IV 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.

Nephrotic-Range Proteinuria and Peripheral Edema in a Child: Not Only Idiopathic Nephrotic Syndrome.

Hemolytic uremic syndrome (HUS) is defined by the simultaneous occurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury due to thrombotic microangiopathy (TMA) mainly occurring in renal and cerebral microvessels. Although the most common cause of HUS in children is Shiga toxin-producing Escherichia coli, atypical forms in which Shiga toxin is not the trigger may occur. Research over the last few years has shown that complement dysregulation secondary to mutations of genes coding for proteins involved in the regulation of the alternative pathway of complement account for most forms of atypical HUS (aHUS). Among these, thrombomodulin (THBD) gene mutations, representing 3-5% of all alternative pathway complement component abnormalities, correlate with early disease onset and rapid evolution to end-stage renal failure. aHUS onset is generally sudden, but occasionally the only manifestations of renal TMA are arterial hypertension, proteinuria, and a progressive increase in serum creatinine. Nephrotic syndrome at disease onset is exceptional. We describe the case of an adolescent female who presented with peripheral edema due to nephrotic-range proteinuria with bioptic evidence of TMA. Study of the alternative complement pathway showed a heterozygous missense THBD gene mutation (P501L variant) consistent with aHUS diagnosis. One year later she developed clinical signs of hemolytic anemia. Eculizumab, an anti-C5 monoclonal antibody, was started with rapid improvement. This case report highlights the phenotypic variability in aHUS due to THBD gene mutation. Early diagnosis by renal biopsy followed by genetic screening is required to optimize management in such a rare disease with a severe prognosis.