Intravenous immunoglobulin treatment for acute attacks in myelin oligodendrocyte glycoprotein antibody disease.

BACKGROUND: The potential therapeutic benefit of intravenous immunoglobulins (IVIGs) for acute attacks of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is unknown. OBJECTIVE: The objective was to describe the outcomes of IVIG treatment for acute MOGAD attacks. METHODS: A retrospective observational study involving seven tertiary neuroimmunology centers. Data collection included patients' demographics, Expanded Disability Status Scale (EDSS), and visual acuity (VA) before the attack, at the nadir of the attack before IVIG treatment, and at follow-up visits ⩾3 months after treatment. RESULTS: Thirty-nine patients were included, of which 21 (53.8%) were female. The median age was 23 years (range 5-74 years), and the median disease duration was 4 months (range 0-93 months). The most common type of attack treated with IVIG was isolated optic neuritis (ON) (unilateral n = 14, bilateral n = 5, associated with transverse myelitis (TM), n = 1), followed by acute disseminated encephalomyelitis (ADEM) (n = 8), multifocal (n = 7), TM (n = 3), brainstem (n = 1), and other encephalitis (n = 1). A significant improvement in both the EDSS and VA measures was observed at follow-up compared to the time of IVIG treatment initiation (p < 0.0001 for both outcome measures). CONCLUSION: IVIG may be an effective treatment option for acute MOGAD attacks. Further prospective studies are warranted to validate our results.

Clinical features, investigations, and outcomes of pediatric limbic encephalitis: A multicenter study.

OBJECTIVES: To describe the clinical presentation, investigations, management, and disease course in pediatric autoimmune limbic encephalitis (LE). METHODS: In this retrospective observational study, from the UK Childhood Neuroinflammatory Disease network, we identified children from six tertiary centers with LE <18 years old between 2008 and 2021. Clinical and paraclinical data were retrieved from medical records. RESULTS: Twenty-five children fulfilling LE criteria were identified, with median age of 11 years (IQR 8, 14) and median follow-up of 24 months (IQR 18, 48). All children presented with seizures; 15/25 (60%) were admitted to intensive care. Neuroimaging demonstrated asymmetric mesial temporal changes in 8/25 (32%), and extra-limbic changes with claustrum involvement in 9/25 (38%). None were positive for LGI1/CASPR2 antibodies (Abs), 2/25 were positive for serum anti-NMDAR Abs, and 2/15 positive for anti-Hu Abs; one died from relapsing neuroblastoma. Two children had serum and CSF anti-GAD antibodies. Initial immune therapy included steroids in 23/25 (92%), intravenous immunoglobulin (IVIg) in 14/25 (56%), and plasma exchange in 7/25 (28%). The commonest second-line treatment was rituximab in 15/25 (60%). Median duration of hospital admission was 21 days (IQR 11, 30). At last follow-up, 13/25 (52%) had refractory seizures and 16/25 (64%) had memory impairment. Six children (24%) had modified Rankin Scale (mRS) scores ≥3. There was no significant difference in mRS, or long-term cognitive and epilepsy outcomes in those who received rituximab versus those who did not. INTERPRETATION: A diagnosis of autoimmune LE was associated with significant morbidity and adverse outcomes in this pediatric cohort.

Incidence of paediatric multiple sclerosis and other acquired demyelinating syndromes: 10-year follow-up surveillance study.

AIM: To describe a 10-year follow-up of children (<16y) with acquired demyelinating syndromes (ADS) from a UK-wide prospective surveillance study. METHOD: Diagnoses were retrieved from the patients' records via the patients' paediatric or adult neurologist using a questionnaire. Demyelinating phenotypes at follow-up were classified by an expert review panel. RESULTS: Twenty-four out of 125 (19.2%) children (64 males, 61 females; median age 10y, range 1y 4mo-15y 11mo), identified in the original study, were diagnosed with multiple sclerosis (incidence of 2.04/million children/year); 23 of 24 fulfilled 2017 McDonald criteria at onset. Aquaporin-4-antibody neuromyelitis optica spectrum disorders were diagnosed in three (2.4%, 0.26/million children/year), and relapsing myelin oligodendrocyte glycoprotein antibody-associated disease in five (4%, 0.43/million children/year). Three out of 125 seronegative patients relapsed and 85 of 125 (68%) remained monophasic over 10 years. Five of 125 patients (4%) originally diagnosed with ADS were reclassified during follow-up: three children diagnosed initially with acute disseminated encephalomyelitis were subsequently diagnosed with acute necrotising encephalopathy (RAN-binding protein 2 mutation), primary haemophagocytic lymphohistiocytosis (Munc 13-4 gene inversion), and anti-N-methyl-d-aspartate receptor encephalitis. One child initially diagnosed with optic neuritis was later diagnosed with vitamin B12 deficiency, and one presenting with transverse myelitis was subsequently diagnosed with Sjögren syndrome. INTERPRETATION: The majority of ADS presentations in children are monophasic, even at 10-year follow-up. Given the implications for treatment strategies, multiple sclerosis and central nervous system autoantibody mimics warrant extensive investigation.

Isolated central nervous system familial hemophagocytic lymphohistiocytosis (fHLH) presenting as a mimic of demyelination in children.

Isolated central nervous system (CNS) presentations of haemophagocytic lymphohistiocytosis (HLH), traditionally a systemic inflammatory condition, have been reported in adults and children. We identified nine patients with a diagnosis of isolated CNS familial hemophagocytic lymphohistiocytosis (fHLH) with symptom onset <18 years of age, and one asymptomatic sibling. Children with atypical chronic/recurrent CNS inflammation should be considered for immunological and genetic panel testing for fHLH even in the absence of any systemic inflammatory features. Despite haematopoietic stem cell transplantation (HSCT) being a mainstay of treatment, treatment failure and high morbidity and mortality post-HSCT suggest that alternative immune therapies may be worth considering.

Is chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in children the same condition as in adults?

This case series describes three children with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), an inflammatory condition characterized by a relapsing-remitting disease course responsive to steroids. The patients (two males, age 3y and 13y; one female, age 14y) presented with ataxia, dysarthria, and multiple cranial neuropathies. All patients demonstrated bilateral nodular lesions with contrast enhancement in the brainstem and cerebellum on magnetic resonance imaging, and perivascular lymphocytes and macrophages infiltrates on brain biopsies. Despite an initially good response to corticosteroids, all patients eventually became steroid-dependent or -resistant, with frequent relapses on maintenance immunosuppressive therapy. Natalizumab and intravenous immunoglobulin stopped neurological disease progression in Patient 1 but he died at 17 years from respiratory complications. Patient 2 went into remission on infliximab and intravenous methylprednisolone for several months but was then diagnosed with Epstein-Barr virus driven B-cell lymphoma 3 years after symptom onset. Patient 3 failed to respond to treatment and died 4 years after diagnosis. CLIPPERS disease in children is aggressive, with poor response to immunotherapy. Earlier use of newer immunotherapeutic agents such as natalizumab may be beneficial. Potential side effects need to be considered carefully. WHAT THIS PAPER ADDS: Paediatric chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) appears a more severe condition than previously reported in adults. Aggressive treatment before neuroaxonal loss may be required for a better outcome.

¿ES LA INFLAMACIÓN LINFOCÍTICA CRÓNICA CON REALCE PERIVASCULAR PONTINO SENSIBLE A LOS ESTEROIDES (CLIPPERS) EN LOS NIÑOS CON LA MISMA CONDICIÓN QUE EN LOS ADULTOS?: Esta serie de casos describe a tres niños con inflamación linfocítica crónica con realce pontinal perivascular sensible a esteroides (CLIPPERS), una enfermedad inflamatoria caracterizada por un curso de enfermedad recurrente-remitente sensible a los esteroides. Los pacientes (dos varones, edad 3 y 13 años, una mujer, edad 14 años) presentaron ataxia, disartria y neuropatías craneales múltiples. Todos los pacientes demostraron lesiones nodulares bilaterales con realce de contraste en el tallo cerebral y el cerebelo en imágenes de resonancia magnética y linfocitos perivasculares y infiltrados de macrófagos en biopsias cerebrales. A pesar de una respuesta inicialmente buena a los corticosteroides, todos los pacientes finalmente se volvieron dependientes de esteroides o resistentes, con recaídas frecuentes en la terapia inmunosupresora de mantenimiento. El natalizumab y la inmunoglobulina intravenosa suspendieron la progresión de la enfermedad neurológica en el paciente 1, pero falleció a los 17 años por complicaciones respiratorias. El paciente 2 entró en remisión con infliximab y metilprednisolona por vía intravenosa durante varios meses, pero luego se le diagnosticó linfoma de células B dirigido por el virus de Epstein-Barr, 3 años después del inicio de los síntomas. El paciente 3 no respondió al tratamiento y murió 4 años después del diagnóstico. La enfermedad de CLIPPERS en los niños es agresiva, con una respuesta deficiente a la inmunoterapia. El uso previo de agentes inmunoterápicos más nuevos como natalizumab puede ser beneficioso. Los posibles efectos secundarios deben considerarse cuidadosamente.

A INFLAMAÇÃO LINFOCÍTICA CRÔNICA COM REALCE PERIVASCULAR PONTINO RESPONSIVA A ESTERÓIDES (CLIPPERS) É A MESMA CONDIÇÃO EM CRIANÇAS E ADULTOS?: Esta série de casos descreve três crianças com inflamação linfocítica crônica com realce perivascular pontino responsiva a esteróides (CLIPPERS), uma condição inflamatória caracterizada por uma doença com curso remissivo-recidivante responsive a esteróides. Os pacientes (dois meninos, idades 3 e 13 anos; uma menina, idade 14 anos) apresentaram ataxia, disartria, e múltiplas neuropatias craniais. Todos os pacientes demonstraram lesões nodulares bilaterais com realce no tronco cerebral e cerebelo ao exame ne ressonância magnética, e infiltrados perivasculares de linfócitos e macrófagos nas biópsias cerebrais. Apesar de uma resposta inicialmente boa aos corticoesteróides, todos os pacientes eventualmente se tornaram esteróide-dependentes ou resistentes, com frequentes recidivas com manutenção de imunoterapia supressora. Natalizumab e imunoglobulina intravenosa interromperam a progressão neurológica da doença no Paciente 1, mas ele veio a óbito na idade de 17 anos devido a complicações respiratórias. O Paciente 2 entrou em remissão com infliximab e metilprednosolona intravenosa por vários meses, mas foi então diagnosticado com linfoma de células B causado por virus Epstein-Barr 3 anos após o início dos sintomas. O Paciente 3 não respondeu ao tratamento e veio a óbito 4 anos após o diagnóstico. Patient 2 went into remission on infliximab and intravenous methylprednisolone for several months but was then diagnosed with Epstein-Barr virus driven B-cell lymphoma 3 years after symptom onset. Patient 3 failed to respond to treatment and died 4 years after diagnosis. INTERPRETAÇÃO: A doença CLIPPERS em crianças é agressiva, com pouca resposta à imunoterapia. O uso precoce de agentes imunoterapêuticos mais novos como natalizumab pode ser benéfico. Potenciais efeitos colaterais devem ser considerados com cautela.

Maternal and perinatal factors associated with hospitalised infectious mononucleosis in children, adolescents and young adults: record linkage study.

BACKGROUND: There is current interest in the role of perinatal factors in the aetiology of diseases that occur later in life. Infectious mononucleosis (IM) can follow late primary infection with Epstein-Barr virus (EBV), and has been shown to increase the risk of multiple sclerosis and Hodgkin's disease. Little is known about maternal or perinatal factors associated with IM or its sequelae. METHODS: We investigated perinatal risk factors for hospitalised IM using a prospective record-linkage study in a population in the south of England. The dataset used, the Oxford record linkage study (ORLS), includes abstracts of birth registrations, maternities and in-patient hospital records, including day case care, for all subjects in a defined geographical area. From these sources, we identified cases of hospitalised IM up to the age of 30 years in people for whom the ORLS had a maternity record; and we compared perinatal factors in their pregnancy with those in the pregnancy of children who had no hospital record of IM. RESULTS: Our data showed a significant association between hospitalised IM and lower social class (p = 0.02), a higher risk of hospitalised IM in children of married rather than single mothers (p < 0.001), and, of marginal statistical significance, an association with singleton birth (p = 0.06). The ratio of observed to expected cases of hospitalised IM in each season was 0.95 in winter, 1.02 in spring, 1.02 in summer and 1.00 in autumn. The chi-square test for seasonality, with a value of 0.8, was not significant.Other factors studied, including low birth weight, short gestational age, maternal smoking, late age at motherhood, did not increase the risk of subsequent hospitalised IM. CONCLUSIONS: Because of the increasing tendency of women to postpone childbearing, it is useful to know that older age at motherhood is not associated with an increased risk of hospitalised IM in their children. We have no explanation for the finding that children of married women had a higher risk of IM than those of single mothers. Though highly significant, it may nonetheless be a chance finding. We found no evidence that such perinatal factors as birth weight and gestational age, or season of birth, were associated with the risk of hospitalised IM.