Aim
To test the hypothesis that children and young people with neurological conditions who missed outpatient appointments have more emergency inpatient admissions and Accident and Emergency centre ...(A&E) visits than those who missed none.
Method
Retrospective cohort of individuals aged up to 19 years with neurological conditions, identified from routine hospital data in England, UK from April 1st, 2003 to March 31st, 2015 using an International Statistical Classification of Diseases and Related Health Problems, coding framework. Counts of emergency inpatient admissions and A&E visits per person per year were modelled (random intercept negative binomial regression) with outpatient attendance the independent variable of interest.
Results
The cohort numbered 524 613 individuals. Those who missed outpatient appointments had 19 per cent (95% confidence interval CI 18–19) more emergency inpatient admissions and 16 per cent (95% CI 15–17) more A&E visits per year than those who missed none. ‘Did not attends’ had a larger increase in unplanned health care than patient or provider cancellations. If no appointments were missed, the models predict there would have been 107 000 fewer A&E visits from 2007/2008 to 2014/2015 and 104 000 fewer emergency inpatient admissions from 2003/2004 to 2014/2015.
Interpretation
Missed outpatient appointments were associated with increased unplanned health care. Improving outpatient attendance may have the potential to reduce emergency inpatient admissions and A&E visits.
What this paper adds
Missed outpatient appointments by children and young people with neurological conditions are associated with increased unplanned health care.
Both emergency inpatient admissions and Accident and Emergency centre visits are increased.
‘Did not attends’ are more strongly associated with unplanned health care than cancellations.
Resumen
Atención ambulatoria sin cita y atención médica no planificada para niños y jóvenes con afecciones neurológicas: un estudio de cohorte retrospectivo
Objetivo
Evaluar la hipótesis de que los niños y los jóvenes con afecciones neurológicas que faltaron a las citas para pacientes ambulatorios tienen más ingresos de pacientes hospitalizados de emergencia, y visitas de accidentes y de emergencia, que aquellos que no faltaron a ninguno.
Método
Cohorte retrospectiva de individuos de hasta 19 años con afecciones neurológicas, identificada a partir de datos hospitalarios de rutina en Inglaterra desde el 1 de abril de 2003 hasta el 31 de marzo de 2015 mediante una Clasificación Internacional de Enfermedades, 10ª Revisión, como marco de codificación. Utilizando modelos estadísticos se consideraron los numeros de ingresos de pacientes hospitalizados de emergencia y las visitas de accidentes y emergencias por persona por año (intercepción aleatoria de regresión binomial negativa) con asistencia ambulatoria como variable independiente de interés.
Resultados
La cohorte incluyo 524.613 individuos. Aquellos que faltaron a las citas para pacientes ambulatorios tuvieron un 19% (95% intervalo de confianza IC 18–19) más hospitalizaciones de emergencia y un 16% (95% CI 15–17) más visitas de accidentes y emergencias por año que aquellos que no faltaron a ninguna. “No asistió” tuvo un aumento mayor en la atención no planificada que las cancelaciones de pacientes o proveedores. Si no se faltara a ninguna cita, los modelos predicen que habría habido 107.000 visitas de accidentes y emergencias menos de 2007/2008 a 2014/2015 y 104.000 menos hospitalizaciones de emergencia para pacientes hospitalizados de 2003/2004 a 2014/2015.
Interpretación
Las citas ambulatorias perdidas se asociaron con una mayor atención no planificada. Mejorar la asistencia ambulatoria puede tener el potencial de reducir las admisiones de pacientes hospitalizados de emergencia y las visitas de accidentes y emergencias.
Resumo
Não‐comparecimento a consultas agendadas e cuidado em saúde não planejado para crianças e jovens com condições neurológicas: um estudo de coorte retrospectivo
Objetivo
Testar a hipótese de que crianças e jovens com condições neurológicas que perderam consultas agendadas têm mais admissões de internações de emergência, de acidentes e visitas de emergência do que os que não perderam nenhuma consulta.
Método
Uma coorte retrospectiva com idade de até 19 anos com condições neurológicas, identificada a partir de dados de rotina de um hospital na Inglaterra de 1 de abril de 2003 a 31 de março de 2015, usando o sistema de códigos da Classificação Internacional de Doenças, 10a edição. Quantidades de admissões em internações de emergência, e visitas de emergência e de acidentes por pessoa por ano foram modeladas (regressão binomial com intercepto aleatório negative), com frequência em consultas sendo a variável de interesse.
Resultados
A coorte atingiu 524.613 indivíduos. Aqueles que perderam consultas agendadas tiveram 19% (intervalo de confiança IC 95% 18–19) mais internações de emergência e 16% (IC 95% 15–17) mais visitas de acidente e emergência por ano do que aqueles que não perderam nenhuma. “Não comparecimentos” tiveram maior aumento de cuidado não planejado do que cancelamentos por parte do paciente ou professional. Se nenhuma consulta fosse perdida, os modelos predizem que haveria 107.000 menos visitas de emergência de 2007/2008 a 2014/2015 e 104.000 menos internações de emergência de 2003/2004 a 2014/2015.
Interpretação
Consultas perdidas foram associadas com aumento de cuidado não planejado. Melhorar a frequência a consultas pode ter o potencial de reduzir internações de emergência e visitas de emergência e de acidentes.
What this paper adds
Missed outpatient appointments by children and young people with neurological conditions are associated with increased unplanned health care.
Both emergency inpatient admissions and Accident and Emergency centre visits are increased.
‘Did not attends’ are more strongly associated with unplanned health care than cancellations.
This article is commented on by Appleton on page 743 of this issue.
This article's has been translated into Spanish and Portuguese.
Follow the links from the to view the translations.
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.
Resumen
¿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.
Resumo
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.
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.
This article's has been translated into Spanish and Portuguese.
Follow the links from the to view the translations.
This article is commented on by Tobin on pages 391–392 of this issue.
Aim
Previous studies suggest a higher prevalence of neurological disease within certain ethnic communities, but have not specifically considered neuromuscular diseases (NMDs). The aim of this study ...was to calculate the prevalence and relationship of NMDs to ethnicity and deprivation status.
Method
We undertook a retrospective case‐note review of those younger than 16 years with a confirmed diagnosis of NMD in a single centre in Yorkshire in 2010.
Results
Two‐hundred and sixty‐one cases were included. The population (0–16y) in Yorkshire was 707 961. The overall prevalence was 36.9 per 100 000 (95% confidence interval CI 34.6–39.1). Dystrophin‐related muscle disease was the most common condition, with a prevalence of 16.9 per 100 000 males (95% CI 14.7–19.1). There was a significant difference between ethnic groups, with a total NMD prevalence of 91.2 per 100 000 (95% CI 81.6–100.7) in the South Asian ethnic group compared with 28.7 per 100 000 (95% CI 26.4–30.9) in the White group. Prevalence of non‐dystrophin‐related NMDs was four times higher in South Asian than in White children. There was a linear relation between increased prevalence and increased deprivation.
Interpretation
This study confirms higher levels of NMD, particularly recessively inherited NMDs within the South Asian population, as well as a link with higher deprivation. This has implications for service provision and resource allocation.
What this study adds
Prevalence of neuromuscular conditions in the paediatric population in Yorkshire was 36.9 per 100 000.
Prevalence in the paediatric South Asian ethnic group was 91.2 per 100 000.
Prevalence of autosomal recessive neuromuscular diseases (NMDs) in the paediatric South Asian group was four times that of the White group.
It confirms an association between higher prevalence of NMDs and higher levels of deprivation.
This article is commented on by Landfeldt on pages 796–797 of this issue.
Objective
To investigate seven congenital myopathy patients from six families: one French Gypsy, one Spanish Gypsy, four British Pakistanis, and one British Indian. Three patients required mechanical ...ventilation from birth, five died before 22 months, one is ventilator‐dependent, but one, at 30 months, is sitting with minimal support. All parents were unaffected.
Methods
The α‐skeletal muscle actin gene (ACTA1) was sequenced. Available muscle biopsies were investigated by standard histological and electron microscopic techniques. The expression of various proteins was determined by immunohistochemistry, western blotting, or both.
Results
Three homozygous ACTA1 null mutations were identified: p.Arg41X in the French patient, p.Tyr364fsX in the Spanish patient, and p.Asp181fsX10 in all five British patients. An absence of α‐skeletal muscle actin protein but presence of α‐cardiac actin was shown in all muscle biopsies examined, with more α‐cardiac actin in the biopsy from the child with the greatest muscle function. Muscle biopsies from all patients exhibited nemaline bodies whereas three also contained zebra bodies.
Interpretation
The seven patients have recessive nemaline myopathy caused by absence of α‐skeletal muscle actin. The level of retention of α‐cardiac actin, the skeletal muscle fetal actin isoform, may determine α‐skeletal muscle actin disease severity. This has implications for possible future therapy. Ann Neurol 2006
Mitochondrial Ca(2+) uptake has key roles in cell life and death. Physiological Ca(2+) signaling regulates aerobic metabolism, whereas pathological Ca(2+) overload triggers cell death. Mitochondrial ...Ca(2+) uptake is mediated by the Ca(2+) uniporter complex in the inner mitochondrial membrane, which comprises MCU, a Ca(2+)-selective ion channel, and its regulator, MICU1. Here we report mutations of MICU1 in individuals with a disease phenotype characterized by proximal myopathy, learning difficulties and a progressive extrapyramidal movement disorder. In fibroblasts from subjects with MICU1 mutations, agonist-induced mitochondrial Ca(2+) uptake at low cytosolic Ca(2+) concentrations was increased, and cytosolic Ca(2+) signals were reduced. Although resting mitochondrial membrane potential was unchanged in MICU1-deficient cells, the mitochondrial network was severely fragmented. Whereas the pathophysiology of muscular dystrophy and the core myopathies involves abnormal mitochondrial Ca(2+) handling, the phenotype associated with MICU1 deficiency is caused by a primary defect in mitochondrial Ca(2+) signaling, demonstrating the crucial role of mitochondrial Ca(2+) uptake in humans.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Significant inconsistencies in respiratory care provision for Duchenne muscular dystrophy (DMD) are reported across different specialist neuromuscular centres in the UK. The absence of robust ...clinical evidence and expert consensus is a barrier to the implementation of care recommendations in public healthcare systems as is the need to increase awareness of key aspects of care for those living with DMD. Here, we provide evidenced-based and/or consensus-based best practice for the respiratory care of children and adults living with DMD in the UK, both as part of routine care and in an emergency.
Initiated by an expert working group of UK-based respiratory physicians (including British Thoracic Society (BTS) representatives), neuromuscular clinicians, physiotherapist and patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK respiratory teams and neuromuscular services, consensus was achieved on these best practice recommendations for respiratory care in DMD.
The resulting recommendations are presented in the form of a flow chart for assessment and monitoring, with additional guidance and a separate chart setting out key considerations for emergency management. The recommendations have been endorsed by the BTS.
These guidelines provide practical, reasoned recommendations for all those managing day-to-day and acute respiratory care in children and adults with DMD. The hope is that this will support patients and healthcare professionals in accessing high standards of care across the UK.
To describe the respiratory trajectories and their correlation with motor function in an international pediatric cohort of patients with type 2 and nonambulant type 3 spinal muscular atrophy (SMA).
...This was an 8-year retrospective observational study of patients in the International SMA Consortium (iSMAc) natural history study. We retrieved anthropometrics, forced vital capacity (FVC) absolute, FVC percent predicted (FVC%P), and noninvasive ventilation (NIV) requirement. Hammersmith Functional Motor Scale (HFMS) and revised Performance of Upper Limb (RULM) scores were correlated with respiratory function. We excluded patients in interventional clinical trials and on nusinersen commercial therapy.
There were 437 patients with SMA: 348 with type 2 and 89 with nonambulant type 3. Mean age at first visit was 6.9 (±4.4) and 11.1 (±4) years. In SMA type 2, FVC%P declined by 4.2%/y from 5 to 13 years, followed by a slower decline (1.0%/y). In type 3, FVC%P declined by 6.3%/y between 8 and 13 years, followed by a slower decline (0.9%/y). Thirty-nine percent with SMA type 2% and 9% with type 3 required NIV at a median age 5.0 (1.8-16.6) and 15.1 (13.8-16.3) years. Eighty-four percent with SMA type 2% and 80% with type 3 had scoliosis; 54% and 46% required surgery, which did not significantly affect respiratory decline. FVC%P positively correlated with HFMS and RULM scores in both subtypes.
In SMA type 2 and nonambulant type 3, lung function declines differently, with a common leveling after age 13 years. Lung and motor function correlated in both subtypes. Our data further define the milder SMA phenotypes and provide information to benchmark the long-term efficacy of new treatments for SMA.
•Second report of TPM2-related recessive phenotype.•A novel homozygous intronic variant, c.564-2A>C, was identified in TPM2 in the patient.•Heterozygous parents were asymptomatic.•Abolishing acceptor ...splice site for exon 6b, results in a level of normal protein.1.
Pathogenic variants in TPM2 have been associated with a variable clinical spectrum, including congenital myopathies and distal arthrogryposis, all but one with dominant inheritance. We report the second case of recessively inherited TPM2-related Escobar variant of multiple pterygium syndrome and congenital myopathy in a patient from a consanguineous family. Ultra-structural examination of the biopsy revealed few cores/mini-cores and sparse nemaline rods. We found a novel homozygous intronic sequence variant, c.564–2A>C in TPM2. This variant is predicted to abolish the consensus acceptor splice site for exon 6b of TPM2 gene. Parents of the proband, both healthy adults with no clinical features, were heterozygous for the variant. Here we establish a homozygous intronic variant in TPM2 as the likely cause of Escobar variant of multiple pterygium syndrome and congenital myopathy, with sparse nemaline rods.
Brown-Vialetto-Van Laere syndrome is a rare neurological disorder with a variable age at onset and clinical course. The key features are progressive ponto-bulbar palsy and bilateral sensorineural ...deafness. A complex neurological phenotype with a mixed picture of upper and lower motor neuron involvement reminiscent of amyotrophic lateral sclerosis evolves with disease progression. We identified a candidate gene,
C20orf54, by studying a consanguineous family with multiple affected individuals and subsequently demonstrated that mutations in this gene were the cause of disease in other, unrelated families.
Subacute Sclerosing Panencephalitis (SSPE) is a fatal progressive neurological disorder following measles infection.
Cases were collated from Paediatric Neurology centres in the UK over 24 months ...from 2017 to 2019 and represent all cases referred to the National Viral Reference Department (VRD). Diagnosis was established with detection of a raised measles index, demonstrating intrathecal measles antibody production.
Six children presented with SSPE over two years, with median age five years (range 2–7 years) and median latency period three years (range 2–6 years). The majority were exposed to measles during infancy. Atypical features were common, including visual impairment, focal and generalised tonic-clonic seizures, headache, vomiting and movement disorders. EEG demonstrated typical features in five cases, though not always at presentation. Initial MRI was normal in four cases, with two showing focal and widespread white matter changes. Antiviral and immunomodulatory treatment led to minimal or no improvement. All progressed to cognitive regression, seizures and neurological decline within six months.
These cases demonstrate the highest incidence of SSPE in the UK since 2000, all progressing to acute fulminant disease, following younger age of onset, short latency period and atypical presentations. Recent global surges in measles cases raise the importance of clinician awareness of SSPE as a potential diagnosis in children with neurological regression. Herd immunity remains the key protective mechanism for infants and groups that cannot be vaccinated. Health care providers, educators and governments must ensure resources continue to target effective education and access to immunisation programmes, the only means to combat this devastating and fatal condition.
•SSPE is a lethal progressive neurological disorder that follows measles infection.•We present the most significant UK cohort in the last 20 years.•Cases were younger than previously described cohorts, with short latency periods.•Acute fulminant course occurred in all, with atypical symptoms and investigations.•The majority were vaccinated, but exposed to measles before the scheduled MMR dose.
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