A recent surge of fulminant and early onset subacute sclerosing panencephalitis (SSPE) in the United Kingdom: An emergence in a time of measles.

BACKGROUND: Subacute Sclerosing Panencephalitis (SSPE) is a fatal progressive neurological disorder following measles infection. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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.

Diagnostic algorithm for children presenting with epilepsia partialis continua.

OBJECTIVE: To characterize a cohort of children with epilepsia partialis continua (EPC) and develop a diagnostic algorithm incorporating key differential diagnoses. METHODS: Children presenting with EPC to a tertiary pediatric neurology center between 2002 and 2019 were characterized. RESULTS: Fifty-four children fulfilled EPC criteria. Median age at onset was 7 years (range 0.6-15), with median follow-up of 4.3 years (range 0.2-16). The diagnosis was Rasmussen encephalitis (RE) in 30 of 54 (56%), a mitochondrial disorder in 12 of 54 (22.2%), and magnetic resonance imaging (MRI) lesion-positive focal epilepsy in 6 of 54 (11.1%). No diagnosis was made in 5 of 54 (9%). Children with mitochondrial disorders developed EPC earlier; each additional year at presentation reduced the odds of a mitochondrial diagnosis by 26% (P = .02). Preceding developmental concerns (odds ratio [OR] 22, P < .001), no seizures prior to EPC (OR 22, P < .001), bilateral slowing on electroencephalogram (EEG) (OR 26, P < .001), and increased cerebrospinal fluid (CSF) protein level (OR 16) predicted a mitochondrial disorder. Asymmetry or hemiatrophy was evident on MRI at presentation with EPC in 18 of 30 (60%) children with RE, and in the remainder at a median of 6 months (range 3-15) after EPC onset. The first diagnostic test is brain MRI. Hemiatrophy may permit a diagnosis of RE with unilateral clinical and EEG findings. For children in whom a diagnosis of RE cannot be made on first scan but the clinical and radiological presentation resembles RE, repeat imaging every 6 months is recommended to detect progressive unicortical hemiatrophy, and brain biopsy should be considered. Evidence of intrathecal inflammation (oligoclonal bands and raised neopterin) can be supportive. In children with bihemispheric EPC, rapid polymerase gamma testing is recommended and if negative, sequencing mtDNA and whole-exome sequencing on blood-derived DNA should be performed. SIGNIFICANCE: Children presenting with EPC due to a mitochondrial disorder show clinical features distinguishing them from RE and structural epilepsies. A diagnostic algorithm for children with EPC will allow targeted investigation and timely diagnosis.

Acquired neuromyotonia in children with CASPR2 and LGI1 antibodies.

Acquired neuromyotonia is a form of peripheral nerve hyperexcitability. In adults, pathogenic antibodies that target the extracellular domains of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) have been reported. We describe three paediatric patients with acquired neuromyotonia and CASPR2 and LGI1 serum antibodies. They all presented with acute-onset myokymia and pain in the lower limbs; one patient also had muscle weakness. Electromyography was suggestive of peripheral nerve hyperexcitability. Two patients improved without immunotherapy; one treated patient remained immunotherapy-dependent. Although not fatal, acquired paediatric neuromyotonia can be disabling. It is amenable to symptomatic treatment or may undergo spontaneous recovery. More severe cases may require rational immunotherapy. WHAT THIS PAPER ADDS: The symptoms of neuromyotonia may resolve spontaneously or may require sodium channel blockers. Patients with debilitating symptoms who are refractory to symptomatic therapy may require immunotherapy.

NEUROMIOTONÍA ADQUIRIDA EN NIÑOS CON ANTICUERPOS CASPR2 Y LGI1: La neuromiotonía adquirida es una forma de hiperexcitabilidad de los nervios periféricos. En algunos adultos, se han notificado anticuerpos patógenos que se dirigen a los dominios extracelulares de la proteína 1 inactivada por glioma rico en leucina (LGI1) y la proteína 2 asociada a contactina (CASPR2). Describimos tres pacientes pediátricos con neuromiotonía adquirida y anticuerpos séricos CASPR2 y LGI1. Todos presentaban mioquimia de inicio agudo y dolor en las extremidades inferiores; un paciente también tenía debilidad muscular. La electromiografía sugirió hiperexcitabilidad del nervio periférico. Dos pacientes mejoraron sin inmunoterapia; un paciente tratado permaneció dependiente de la inmunoterapia. Aunque no es fatal, la neuromiotonía pediátrica adquirida puede ser incapacitante. Es susceptible de tratamiento sintomático o puede sufrir una recuperación espontánea. Los casos más graves pueden requerir inmunoterapia racional.

NEUROMIOTONIA ADQUIRIDA EM CRIANÇAS COM ANTICORPOS PRCAS2 E GIL1: A neuromiotonia adquirida é uma forma de hiperexcitabilidade nervosa periférica. Em alguns adultos, anticorpos patogênicos que visam os domínios extracelulares da proteína glioma-inativada rica em leucina1 (GIL1) e da proteína contactina-associada 2 (PRCAS2) foram reportados. Descrevemos três pacientes pediátricos com neuromiotonia adquirida e anticorpos séricos PRCAS2 e GIL1 CASPR2. Todos apresentaram miocimia de início agudo e dor nos membros inferiores; um paciente também teve fraqueza muscular. A eletromiografia foi sugestiva de hiperexcitabilidade nervosa periférica. Dois pacientes melhoraram sem imunoterapia; um paciente tratado permaneceu imunoterapia-dependente. Embora não seja fatal, a neuromiotomia pediátrica aguda pode ser incapacitante. É responsiva a tratamento sintomático e pode apresentar recuperação espontânea. Casos mais severaos podem requerer imunoterapia racional.

Holt-Oram Syndrome Associated with Aortic Atresia: A Rare Association.

Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder that causes abnormalities of the upper limbs and heart. It is seen in 1:1, 00, 000 live births. It is linked to a single-gene TBX5 "protein-producing" mutation with gene map locus 12q24. Most commonly it is characterized by the cardiac septation defects and pre-axial radial ray abnormalities. We are reporting a case of HOS with aortic atresia which is a rare association.