Investigating the 2023 MOGAD Criteria in Children and Adults With MOG-Antibody Positivity Within and Outside Attacks.

BACKGROUND AND OBJECTIVES: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. METHODS: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure. RESULTS: A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100]). DISCUSSION: The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.

Design and Interrater Reliability of the Pediatric Version of the Race Scale: PedRACE.

BACKGROUND: Acute ischemic stroke is a leading cause of pediatric death and disability. A clinical scale adapted for children can ensure early detection of candidates for urgent acute ischemic stroke treatment. The Rapid Arterial Occlusion Evaluation (RACE) scale for adults, which scores 5 items (facial palsy 0-2; arm motor function 0-2; leg motor function 0-2; head/gaze deviation 0-1; and aphasia or agnosia 0-2), has good sensitivity and specificity in detecting large vessel occlusion. METHODS: We adapted the previously validated RACE scale for use in children as the Pediatric RACE scale. This adapted scale was tested by prehospital/emergency room staff attending to patients covered by the Catalan Pediatric Stroke Code and child neurologists for its correlation with the Pediatric National Institutes of Health Stroke Scale and for interrater reliability. RESULTS: The study included 50 children, 18 with confirmed strokes (7 acute ischemic strokes and 11 hemorrhagic strokes). Prehospital/emergency staff and child neurologists agreed fully regarding 82% of patients and 100% regarding head/gaze deviation and agnosia. The Pediatric RACE scale correlated strongly with the Pediatric National Institutes of Health Stroke Scale in evaluations by child neurologists (Spearman ρ, 0.852; P<0.001) and prehospital/emergency staff (Spearman ρ, 0.781; P<0.001). The median Pediatric RACE score was significantly higher in patients with large vessel occlusion (6.5; interquartile range, 6-7) than with other etiologies. CONCLUSIONS: Pediatric RACE, showing good interrater reliability and correlation with the Pediatric National Institutes of Health Stroke Scale, is a simple scale to detect candidates for pediatric acute stroke treatment, designed for both prehospital and in-hospital use by non-neurologist medical staff.

Impact of COVID-19 in Immunosuppressed Children With Neuroimmunologic Disorders.

BACKGROUND AND OBJECTIVES: To investigate whether children receiving immunosuppressive therapies for neuroimmunologic disorders had (1) increased susceptibility to SARS-CoV2 infection or to develop more severe forms of COVID-19; (2) increased relapses or autoimmune complications if infected; and (3) changes in health care delivery during the pandemic. METHODS: Patients with and without immunosuppressive treatment were recruited to participate in a retrospective survey evaluating the period from March 14, 2020, to March 30, 2021. Demographics, clinical features, type of immunosuppressive treatment, suspected or confirmed COVID-19 in the patients or cohabitants, and changes in care delivery were recorded. RESULTS: One hundred fifty-three children were included: 84 (55%) female, median age 13 years (interquartile range [8-16] years), 79 (52%) on immunosuppressive treatment. COVID-19 was suspected or confirmed in 17 (11%) (all mild), with a frequency similar in patients with and without immunosuppressive treatment (11/79 [14%] vs 6/74 [8%], p = 0.3085). The frequency of neurologic relapses was similar in patients with (18%) and without (21%) COVID-19. Factors associated with COVID-19 included having cohabitants with COVID-19 (p < 0.001) and lower blood levels of vitamin D (p = 0.039). Return to face-to-face schooling or mask type did not influence the risk of infection, although 43(28%) children had contact with a classmate with COVID-19. Clinic visits changed from face to face to remote for 120 (79%) patients; 110 (92%) were satisfied with the change. DISCUSSION: In this cohort of children with neuroimmunologic disorders, the frequency of COVID-19 was low and not affected by immunosuppressive therapies. The main risk factors for developing COVID-19 were having cohabitants with COVID-19 and low vitamin D levels.

Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study.

BACKGROUND: Investigations of myelin oligodendrocyte glycoprotein (MOG) antibodies are usually focused on demyelinating syndromes, but the entire spectrum of MOG antibody-associated syndromes in children is unknown. In this study, we aimed to determine the frequency and distribution of paediatric demyelinating and encephalitic syndromes with MOG antibodies, their response to treatment, and the phenotypes associated with poor prognosis. METHODS: In this prospective observational study, children with demyelinating syndromes and with encephalitis other than acute disseminated encephalomyelitis (ADEM) recruited from 40 secondary and tertiary centres in Spain were investigated for MOG antibodies. All MOG antibody-positive cases were included in our study, which assessed syndromes, treatment and response to treatment (ie, number of relapses), outcomes (measured with the modified Rankin scale [mRS]), and phenotypes associated with poor prognosis. We used Fisher's exact and Wilcoxon rank sum tests to analyse clinical features, and survival Cox regression to analyse time to antibody negativity. FINDINGS: Between June 1, 2013, and Dec 31, 2018, 239 children with demyelinating syndromes (cohort A) and 296 with encephalitis other than ADEM (cohort B) were recruited. 116 patients had MOG antibodies, including 94 (39%) from cohort A and 22 (7%) from cohort B; 57 (49%) were female, with a median age of 6·2 years (IQR 3·7-10·0). Presenting syndromes in these 116 patients included ADEM (46 [68%]), encephalitis other than ADEM (22 [19%]), optic neuritis (20 [17%]), myelitis (13 [11%]), neuromyelitis optica spectrum disorders (six [5%]), and other disorders (nine [8%]). Among the patients with autoimmune encephalitis in cohort B (n=64), MOG antibodies were more common than all neuronal antibodies combined (22 [34%] vs 21 [33%]). After a median follow-up of 42 months (IQR 22-67), 33 (28%) of the 116 patients had relapses, including 17 (17%) of 100 diagnosed at first episode. Steroids, intravenous immunoglobulin, or plasma exchange were used in 100 (86%) patients at diagnosis, and 32 (97%) of 33 at relapses. Rituximab was mainly used at relapses (11 [33%]). 99 (85%) of 116 patients had substantial recovery (mRS <2) and 17 (15%) moderate to severe deficits (mRS >2; one died). Phenotypes of poor prognosis included ADEM-like relapses progressing to leukodystrophy-like features, and extensive cortical encephalitis evolving to atrophy. Time to antibody negativity was longer in patients with relapses (HR 0·18, 95% CI 0·05-0·59). INTERPRETATION: The spectrum of paediatric MOG antibody-associated syndromes is wider than previously reported and includes demyelinating syndromes and encephalitis. Recognition of these disorders has important clinical and prognostic implications. FUNDING: Mutua Madrileña Foundation; ISCIII-Subdirección General de Evaluación y Fomento de la Investigación Sanitaria; Fondo Europeo de Desarrollo Regional; Pediatrics Spanish Society; Departament de Salut, Generalitat de Catalunya; Marato TV3 Foundation; Red Española de Esclerosis Múltiple; La Caixa Foundation; and Fundació CELLEX.

Anti-MOG encephalitis mimicking small vessel CNS vasculitis.

Objective: To report 2 patients with anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis who were initially misdiagnosed with small vessel primary CNS vasculitis. Methods: Review of symptoms, MRI and neuropathologic features, and response to treatment. MOG antibodies were determined in serum and CSF using a cell-based assay. Results: Symptoms included fever, headache, and progressive mental status changes and focal neurologic deficits. CSF studies revealed lymphocytic pleocytosis, and both patients had abnormal brain MRIs. Brain biopsy samples showed prominent lymphocytic infiltration of the wall of small vessels; these findings initially suggested small vessel CNS vasculitis, and both patients were treated accordingly. Although 1 patient had a relapsing-remitting course not responsive to cyclophosphamide, the other one (also treated with cyclophosphamide) did not relapse. Retrospective assessment of serum and CSF demonstrated MOG antibodies in both cases, and review of biopsy specimens showed absence of fibrinoid necrosis (a pathologic requirement for small vessel CNS vasculitis). Conclusions: Anti-MOG-associated encephalitis can be mistaken for small vessel CNS vasculitis. This is important because the diagnosis of anti-MOG-associated encephalitis does not require brain biopsy and can be established with a serologic test.

HaNDL syndrome in a 14-year-old girl.

Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL syndrome) consists of recurrent headaches with focal neurological signs, which can include motor, sensory and aphasic symptoms. Although considered rare, it is becoming increasingly recognised in clinical practice due to the accumulation of case reports. The pathophysiology remains unclear although changes in the neurovascular resemble those found in migraine, which are thought to be triggered by an infectious process. HaNDL can mimic various serious, including life-threatening, diseases, such as stroke and meningoencephalitis, which is why vigorous tests should be sought before this diagnosis of exclusion can be reached. Treatment is symptomatic and the prognosis is excellent. A literature review of the topic is discussed. We report an adolescent girl who presented with recurrent expressive dysphasia and right-sided hypoaesthesia and moderate occipital headaches who was diagnosed with HaNDL syndrome.

Carbamacepina como tratamiento sintomático de las mioclonías en la panencefalitis esclerosante subaguda / Carbamazepine as treatment for the symptoms of myoclonias in subacute sclerosing panencephalitis

No disponible

Vanishing white matter disease in a spanish population.

Vanishing white matter (VWM) leukoencephalopathy is one of the most prevalent hereditary white matter diseases. It has been associated with mutations in genes encoding eukaryotic translation initiation factor (eIF2B). We have compiled a list of all the patients diagnosed with VWM in Spain; we found 21 children. The first clinical manifestation in all of them was spasticity, with severe ataxia in six patients, hemiparesis in one child, and dystonic movements in another. They suffered from progressive cognitive deterioration and nine of them had epilepsy too. In four children, we observed optic atrophy and three also had progressive macrocephaly, which is not common in VWM disease. The first two cases were diagnosed before the 1980s. Therefore, they were diagnosed by necropsy studies. The last 16 patients were diagnosed according to genetics: we found mutations in the genes eIF2B5 (13 cases), eIF2B3 (2 cases), and eIF2B4 (1 case). In our report, the second mutation in frequency was c.318A>T; patients with this mutation all followed a slow chronic course, both in homozygous and heterozygous states. Previously, there were no other reports to confirm this fact. We also found some mutations not described in previous reports: c.1090C>T in eIF2B4, c.314A>G in eIF2B5, and c.877C>T in eIF2B5.

¿Se debe ser más intervencionista en urgencias con las convulsiones febriles atípicas? Experiencia en un hospital terciario durante tres años / Should a more interventionist approach be taken in A&E departments with atypical febrile seizures? Three years’ experience in a tertiary hospital

Introducción. Se han relacionado las convulsiones febriles atípicas (CFA) con una mayor incidencia de patología grave del sistema nervioso central (SNC). Estudios recientes muestran una disminución de la prevalencia de algunas de estas enfermedades, hecho que podría modificar su manejo. Objetivos. Determinar la prevalencia de patología grave del SNC en pacientes atendidos en urgencias por CFA y detectar diferencias con los pacientes con CFA no asociada a patología grave. Pacientes y métodos. Estudio retrospectivo mediante revisión de historias clínicas de los pacientes con diagnóstico de CFA entre noviembre de 2008 y noviembre de 2011. Resultados. Se incluyen 231 episodios de CFA (223 pacientes), con una edad media de 1,7 años (p25-75 = 1,2-2,3 años), 133 (57,6%) de los cuales eran varones. Doce pacientes (5,2%; IC 95% = 2,7-8,9) recibieron el diagnóstico de patología grave del SNC. En los pacientes con patología grave del SNC, la CFA es en la mayoría de las ocasiones el primer episodio (91,7% frente a 63%; p = 0,036), presenta más de un criterio diagnóstico (50% frente a 15,1%; p = 0,007), es más frecuente la convulsión focal (50% frente a 12,8%; p = 0,003) o el estado epiléptico (25% frente a 5,9%; p = 0,041) y los pacientes presentan alteración de la consciencia persistente posterior al episodio (66,7% frente a 31,5%; p = 0,002). Conclusiones. Dado que la prevalencia de patología grave del SNC en pacientes con CFA es baja, no se recomienda la realización rutinaria de pruebas complementarias ni el ingreso. Determinadas características del episodio aumentan la probabilidad de que la CFA sea la manifestación de una patología grave del SNC (ser un primer episodio, presentar más de un criterio diagnóstico de CFA y tratarse de una convulsión focal o estado epiléptico), por lo que deberían tenerse en cuenta en el manejo del paciente (AU)

Introduction. Atypical febrile seizures (AFS) have been related with a higher incidence of severe pathologies of the central nervous system (CNS). Recent studies show a reduction in the prevalence of some of these diseases, a fact that could affect their management. Aims. To determine the prevalence of severe pathologies of the CNS in patients treated for AFS in A&E departments and to detect any differences between these and patients suffering from AFS that is not associated to any severe pathology. Patients and methods. A retrospective study was conducted by reviewing the medical records of patients diagnosed with AFS between November 2008 and November 2011. Results. Altogether, the sample consisted of 231 episodes of AFS (223 patients), with an average age of 1.7 years (p25-75 = 1.2-2.3 years), 133 (57.6%) of whom were males. Twelve patients (5.2%; 95% CI = 2.7-8.9) were diagnosed with a severe pathology of the CNS. In patients with a severe pathology of the CNS, AFS is on most occasions the first episode (91.7% versus 63%; p = 0.036) and more than one diagnostic criterion is present (50% versus 15.1%; p = 0.007). Moreover, focal seizures (50% versus 12.8%; p = 0.003) or epileptic status (25% versus 5.9%; p = 0.041) are more common, and patients present altered levels of awareness that persist after the episode (66.7% versus 31.5%; p = 0.002). Conclusions. Given the fact that the prevalence of severe pathology of the CNS in patients with AFS is low, carrying out complementary tests or admission to hospital on a routine basis are not recommended. Certain characteristics of the episode increase the likelihood of AFS being the manifestation of a severe pathology of the CNS (being a first episode, presenting more than one diagnostic criterion for AFS and being a focal seizure or epileptic status), and should therefore be taken into account in the management of the patient (AU)

[Should a more interventionist approach be taken in A and E departments with atypical febrile seizures? Three years' experience in a tertiary hospital]. / Se debe ser más intervencionista en urgencias con las convulsiones febriles atípicas? Experiencia en un hospital terciario durante tres años.

INTRODUCTION: Atypical febrile seizures (AFS) have been related with a higher incidence of severe pathologies of the central nervous system (CNS). Recent studies show a reduction in the prevalence of some of these diseases, a fact that could affect their management. AIMS. To determine the prevalence of severe pathologies of the CNS in patients treated for AFS in A and E departments and to detect any differences between these and patients suffering from AFS that is not associated to any severe pathology. PATIENTS AND METHODS: A retrospective study was conducted by reviewing the medical records of patients diagnosed with AFS between November 2008 and November 2011. RESULTS: Altogether, the sample consisted of 231 episodes of AFS (223 patients), with an average age of 1.7 years (p25-75=1.2-2.3 years), 133 (57.6%) of whom were males. Twelve patients (5.2%; 95% CI=2.7-8.9) were diagnosed with a severe pathology of the CNS. In patients with a severe pathology of the CNS, AFS is on most occasions the first episode (91.7% versus 63%; p=0.036) and more than one diagnostic criterion is present (50% versus 15.1%; p=0.007). Moreover, focal seizures (50% versus 12.8%; p=0.003) or epileptic status (25% versus 5.9%; p=0.041) are more common, and patients present altered levels of awareness that persist after the episode (66.7% versus 31.5%; p=0.002). CONCLUSIONS: Given the fact that the prevalence of severe pathology of the CNS in patients with AFS is low, carrying out complementary tests or admission to hospital on a routine basis are not recommended. Certain characteristics of the episode increase the likelihood of AFS being the manifestation of a severe pathology of the CNS (being a first episode, presenting more than one diagnostic criterion for AFS and being a focal seizure or epileptic status), and should therefore be taken into account in the management of the patient.

Vertical ophthalmoplegia due to a unilateral periaqueductal gray matter infarct in an adolescent.

Brainstem strokes affecting the periaqueductal gray matter of the midbrain can cause vertical ophthalmoplegia. Accompanying clinical features are frequently associated and reflect the involvement of other brainstem structures. We report on an adolescent presenting with vertical gaze palsy and left mydriatic pupil as the only clinical expression of a small infarct located in the left periaqueductal gray matter. Even when the lesion was strictly unilateral, vertical ophthalmoplegia affected both eyes.

[Dissections of craniocervical arteries in the paediatric age: a pathology that is emerging or under-diagnosed?]. / Disecciones arteriales craneocervicales en la edad pediátrica: una patología emergente o infradiagnosticada?

INTRODUCTION: Cranio-cervical arterial dissections are a recognized cause of ischemic stroke in childhood, with an approximate incidence of 0.4 to 20%. AIM. To describe a population of children with cranio-cervical arterial dissections, analyzing clinical presentation, risk factors, angiographic findings, evolution and treatment. PATIENTS AND METHODS: A descriptive, retrospective, longitudinal collaborative review (Sant Joan de Deu and Pereira Rossell Children's Hospital), of children one month to 17 years old of age was conducted, during the period of time between 2000 to 2009. RESULTS: Ten cases with arterial dissection were identified, 7 of them were boys and 3 girls. Nine had a traumatism preceding neurological symptoms. Clinical presentation included 5 patients with hemiparesis, 3 with hemicerebelus syndrome, 1 with VI cranial nerve palsy and 1 with intracranial soplus as the only symptom at physical examination. Three of them had seizures, while headache preceding the onset of cerebral ischemic symptoms was founded in 6 of them. Dissection involved anterior circulation in 5 patients and posterior circulation in the other 5. In reference to the localization of arterial compromise 4 patients had intracranial dissections and 6 had extracranial dissections. Anticoagulation therapy was done in 5, antiagregation in 3, and treatment abstention in two. None of them suffered neither complications due to anticoagulation therapy nor dead or recurrent dissections in long term follow up (2 months to 8 years). CONCLUSIONS: Cranio-cervical dissections are a frequent cause of stroke in childhood. Clinical suspicious related to cranio-cervical traumatisms and subsequent neurological symptoms should be high.

Disecciones arteriales craneocervicales en la edad pediátrica: ¿una patología emergente o infradiagnosticada? / Dissections of craniocervical arteries in the paediatric age: a pathology that is emerging or under-diagnosed?

Introducción. Las disecciones craneocervicales constituyen una reconocida causa de ictus en la infancia y adolescencia, y son responsables del 0,4-20% del total de casos. Objetivo. Describir una población de niños con disecciones arteriales, analizando su presentación clínica, factores de riesgo, signos angiográficos, evolución y tratamiento. Pacientes y métodos. Se llevó a cabo un estudio descriptivo, retrospectivo y colaborativo (Hospital Sant Joan de Déu de Barcelona y Centro Hospitalario Pereira Rossell de Montevideo), durante los años 2000 a 2009, de niños entre 1 mes a 17 años, con disecciones arteriales craneocervicales. Resultados. Se identificaron 10 casos con diagnóstico de disección arterial, siete varones y tres niñas. Nueve presentaron traumatismo previo al inicio de los síntomas neurológicos. Del total de pacientes, cinco comenzaron con hemiparesia, tres con síndrome hemicerebeloso, uno con afectación del VI par, y uno con soplo craneal. De éstos, tres tuvieron convulsiones y seis cefaleas que precedieron al cuadro clínico. El deterioro de la circulación anterior tuvo lugar en cinco niños, y l de la posterior en los otros cinco. Cuatro pacientes presentaron afectación arterial intracraneal, y seis, extracraneal. Se realizó anticoagulación en cinco pacientes, antiagregación en tres y no se trataron los dos restantes. No hubo fallecimientos, complicaciones por la anticoagulación, ni recurrencias en el período de seguimiento clínico. Conclusiones. Las disecciones craneocervicales son una causa frecuente de ictus en la infancia. La sospecha clínica debe ser alta ante todo paciente con sintomatología focal neurológica en relación con un traumatismo craneocervical (AU)

Introduction. Cranio-cervical arterial dissections are a recognized cause of ischemic stroke in childhood, with an approximate incidence of 0.4 to 20%. Aim. To describe a population of children with cranio-cervical arterial dissections, analyzing clinical presentation, risk factors, angiographic findings, evolution and treatment. Patients and methods. A descriptive, retrospective, longitudinal collaborative review (Sant Joan de Déu and Pereira Rossell Children’s Hospital), of children one month to 17 years old of age was conducted, during the period of time between 2000 to 2009. Results. Ten cases with arterial dissection were identified, 7 of them were boys and 3 girls. Nine had a traumatism preceding neurological symptoms. Clinical presentation included 5 patients with hemiparesis, 3 with hemicerebelus syndrome, 1 with VI cranial nerve palsy and 1 with intracranial soplus as the only symptom at physical examination. Three of them had seizures, while headache preceding the onset of cerebral ischemic symptoms was founded in 6 of them. Dissection involved anterior circulation in 5 patients and posterior circulation in the other 5. In reference to the localization of arterial compromise 4 patients had intracranial dissections and 6 had extracranial dissections. Anticoagulation therapy was done in 5, antiagregation in 3, and treatment abstention in two. None of them suffered neither complications due to anticoagulation therapy nor dead or recurrent dissections in long term follow up (2 months to 8 years). Conclusions. Cranio-cervical dissections are a frequent cause of stroke in childhood. Clinical suspicious related to craniocervical traumatisms and subsequent neurological symptoms should be high (AU)