•Newborn screening for SMA is performed today in 9 countries.•Fewer than 2% of the newborns of the whole world are currently screened for SMA.•Respondents are moderately optimistic about NBS ...development over the next 4 years.•Lack of cost/benefit data is identified as a key obstacle for wider implementation.
Spinal muscular atrophy (SMA) is a rare and devastating disease. New disease-modifying treatments have recently been approved and early treatment has been related to a better outcome. In this context, several newborn screening (NBS) programs have been implemented. The aim of the study was to obtain a global overview on the current situation and perspectives on SMA NBS. We conducted a survey and contacted experts from 152 countries, from which we gathered 87 responses. We identified 9 SMA NBS programs that have so far detected 288 newborns with SMA out of 3,674,277 newborns screened. Funding, screening methods, organisation, and consent process were variable between SMA NBS programs. Many respondents pointed the lack of cost/benefit data as a major obstacle to SMA NBS implementation. In the next four years, our data suggest a 24% coverage of newborns from countries where a disease-modifying drug is available and 8,5% coverage in countries with no diseases-modifying drugs. The annual proportion of newborns to be screened in the coming years is expected to increase steadily. The experts expressed a strong need for the implementation of SMA NBS as means to improve care for patients with SMA.
Abstract Objective evaluation of etiology, clinical course and response to the treatment of status epilepticus (SE) in children, with particular investigation of superrefractory SE. Materials and ...methods The retrospective study included children with convulsive SE aged 0.2–18 years, treated from 1995 to 2011. Status epilepticus is defined as a continuous seizure or intermittent seizures without full recovery of consciousness between seizures for at least 30 min. Refractory SE is diagnosed if SE lasts for more than 60 min, while superrefractory SE if SE continues or recurs 24 h or more after the onset of an anesthesia therapy, including those cases that recur after reduction or withdrawal of an anesthesia. The etiology was summarized in five categories: idiopathic/cryptogenic, remote symptomatic, febrile SE, acute symptomatic and progressive encephalopathy. The patients were treated according to the same hospital protocol. Midazolam iv and diazepam rectally were given as the first line drugs, phenobarbital/phenytoin iv as the second line drugs. If they failed, third line drugs, midazolam and thiopental were given in continuous intravenous infusion. The medication was defined as effective if seizure clinically stopped within 20 min, without recurrence within the next 6 h. Midazolam was assessed as effective even if it failed as the first line, but was effective in intravenous infusion as the third line drug. Results The study consisted of 602 SE in 395 children. There were 305 (50.7%) refractory SE episodes, and 43 (7.1%) of superrefractory SE. Idiopathic/cryptogenic and febrile SE was the most common etiology in the first SE, while progressive encephalopathy and remote symptomatic was in recurrent and superrefractory SE. The most effective drugs were: midazolam (306/339) given in mean dose of 0.4 mg/kg (range 0.1–1.2 mg/kg), thiopental (47/57) in mean dose of 4 mg/kg (range 3–5 mg/kg), phenobarbital (91/135) in dose of 20 mg/kg. Midazolam successfully stopped 306/339 SE episodes (90.3%), 67 SE (21.9%) by equal or lower dose than 0.2 mg/kg as the first line drug, while all other 239 episodes (78.9%) were stopped by intravenous infusion in range 0.2–1.2 mg/kg/h (mean 0.4 mg/kg/h) as the third line drug. Adverse effects were frequent in superrefractory SE (60.5%). In 15 patients, corticosteroids contributed to the reduction of seizure recurrence after anesthetic withdrawal and cessation of epilepsia partialis continua. Case fatality rate was 5.1% in all patients, while 21.3% in patients with superrefractory SE. Conclusion Status epilepticus in children was characterized by heterogeneous etiology, prolonged duration and commonly good response to midazolam only given in high doses. Superrefractory SE was not so rare in children, especially among the patients with progressive encephalopathy.
•Congenital myotonic dystrophy type 1 (CMD1) is a rare neuromuscular disease.•CDM1 is characterized by neonatal hypotonia, weakness, feeding and respiratory difficulties.•Many CMD1 patients suffer ...from hypoxic ischemic encephalopathy (HIE).•HIE, preterm delivery, resuscitation and hypothermia treatment are poor prognostic factors for survival.•Respiratory insufficiency is the main life-threatening factor in CDM1.
Congenital myotonic dystrophy type 1 (CDM1) is a rare neuromuscular disease. The aim of our study was to evaluate clinical variability of CDM1 and factors that may influence survival in CDM1. Research included 24 pediatric patients with CDM1. Most of our patients had some form of hypoxic ischemic encephalopathy (HIE) (74 %), from mild to severe. Prolonged and complicated deliveries (75 %), high percentage of children resuscitated at birth (57 %) and respiratory insufficiency (46 %) with consequent hypoxia were the main reasons that could explain high percentage of HIE. Therapeutic hypothermia was applied in three children with poor outcome. Median survival of all CDM1 was 14.2 ± 1.5 years. Six patients had a fatal outcome (25 %). Their mean age of death was 3.0 ± 2.8 years. Poor prognostic factors for the survival of our CDM1 patients were: preterm delivery, resuscitation at birth, severe HIE, hypothermia treatment and permanent mechanical ventilation. Respiratory insufficiency was the main life-threatening factor. Our data clearly indicates the need to develop natural history studies in CDM1 in order to enhance the standards of care and to develop clinical trials investigating causative therapies in pediatric patients with CDM1.
Introduction. Hemorrhagic shock and encephalopathy syndrome (HSES) is a rare disorder with prevalence at an early age. The main features of HSES are acute diarrhea, shock, disseminated intravascular ...coagulation, multisystem impairment, and encephalopathy. The prognosis is very poor, with high mortality, especially in cases with status epilepticus. Case outline. The presented infant had typical features of HSES associated with super-refractory status epilepticus as de novo epileptic event, followed by pharmacoresistant epilepsy. Clinical course of the disease was very severe and required urgent circulatory and respiratory support, and simultaneous management of super-refractory status epilepticus by continuous intravenous infusion of midazolam, barbiturate, and levetiracetam. The outcome was very poor with serious neurological consequence and resistant epileptic seizures. Conclusion. The treatment of the presented patient with HSES was very challenging due to a lifethreatening condition associated with super-refractory status epilepticus, and further pharmacoresistant epilepsy. Additionally, the choice of antiepileptic drugs is limited due to multisystem impairment and adverse effects which might worsen the already severe course of the disease.
Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare pediatric neurodegenerative condition, which is usually fatal by mid-adolescence. Seizures are one of the most common early symptoms of ...CLN2 disease, but patients often experience language deficits, movement disorders, and behavioral problems. Diagnosis of CLN2 disease is challenging (particularly when differentiating between early-onset developmental, metabolic, or epileptic syndromes), and diagnostic delays often overlap with rapid disease progression. An enzyme replacement therapy (cerliponase alfa) is now available, adding CLN2 disease to the list of potentially treatable disorders requiring a prompt diagnosis.
Although advances in enzymatic activity testing and genetic testing have facilitated diagnoses of CLN2 disease, our review highlights the presenting symptoms that are vital in directing clinicians to perform appropriate tests or seek expert opinion. We also describe common diagnostic challenges and some potential misdiagnoses that may occur during differential diagnosis.
An awareness of CLN2 disease as a potentially treatable disorder and increased understanding of the key presenting symptoms can support selection of appropriate tests and prompt diagnosis. The available enzyme replacement therapy heralds an even greater imperative for early diagnosis, and for clinicians to direct patients to appropriate diagnostic pathways.
Introduction/Objective. Acute disseminated encephalomyelitis (ADEM) is the most common demyelinating disease of the central nervous system in pediatric patients. We aimed to evaluate the clinical ...profile of children with ADEM and to discern prognostic factors for disease outcome. Methods. A 20-year retrospective?prospective study was conducted in a cohort with the diagnosis of ADEM. Results. The study included 36 patients, with range of follow-up period of 6?120 months (median of 26 months). Prior infection was reported in 72.2% of the patients. In the clinical presentation of the disease, motor deficit was most common (81.1%), followed by ataxia (77.8%). More than a third of patients had back and limb pain or abdominal visceral pain, which highly correlated with MRI findings of myelitis. Abnormal brain CT findings were evident in 22.2% of the patients, and this was associated with higher Expanded Disability Status Scale (EDSS) and quicker progression of the disease. Median EDSS was 0 at the most recent follow-up visit, in all the patients. EDSS 0?2.5 was verified in 29 (80.6%) of the patients, while three (8.3%) patients scored 7?9.5 at the last visit. Two patients had a lethal outcome. Conclusions. ADEM is a serious disease in pediatric patients, but with a good prognosis, which is illustrated by the fact that 80.6% of our patients had a complete or almost complete recovery.
The aim of this study was to evaluate the predictive value of the features of neonatal seizures for pharmacoresistant epilepsy in children.
This is a retrospective study that involved all children ...diagnosed as having epilepsy who had neonatal seizures and who were hospitalized at the Neurology Department of the Mother and Child Healthcare Institute in Belgrade from January the 1st 2017 until December 31st 2017. The following parameters and their impact on the outcome were investigated: perinatal data, the characteristics of epileptic seizures in the neonatal period, and the response to anticonvulsant treatment. The presence of pharmacoresistance was observed as an outcome parameter. Univariate and multivariate logistic regression analyses were used to define predictors of drug-resistant epilepsy.
The study involved 55 children, 35 (63.6%) male and 20 (36.4%) female. The average age of the children at the end of the observation period was 5.17 years (min: 0.25, max: 17.75, iqr (interquartile range): 6.92). Pharmacoresistant epilepsy was found in 36 (65.5%) children. The most common type of epilepsy was focal, which affected 30 patients (54.5%), than generalized, which affected 15 patients (27.3%), and combined generalized and focal, which affected 8 patients (14.5%). At the end of the observation period, 28 patients (50.9%) had no seizures, while 14 (25.5%) had daily seizures. It was found that the pharmacoresistant neonatal seizures and metabolic–genetic disorders were predictive factors of the occurrence of pharmacoresistant epilepsy.
Patients prone to developing pharmacoresistant epilepsy might be identified as early as the neonatal and early infant period. High incidence of asphyxia cooccurring with established genetic–metabolic disease further emphasizes need for genetic testing in infants with neonatal seizures including in the presence of hypoxic–ischemic injury.
•The study involved 55 children, 35 (63.6%) male and 20 (36.4%) female.•Pharmacoresistant epilepsy was found in 36 (65.5%) children.•Patients prone to developing pharmacoresistant epilepsy can be identified as early as the neonatal and early infant age.•A poor seizure control, inborn errors of metabolism and genetic disorders are predictive factors.
Introduction. Coronavirus disease-2019 (COVID-19) usually leads to a mild infectious disease course in children, but serious neurological complications have been described in association with both ...acute infection and the multisystem inflammatory syndrome in children (MIS-C). Cerebrovascular disorders (CVD) in children are rare complication of MIS-C, and various potential mechanisms of CVD in MIS-C have been hypothesized. Case outline. In an eight-year old girl, diagnosis of MIS-C was made according to clinical features of prolonged fever, circulatory shock, heart and renal insufficiency, skin abnormalities, conjunctival hyperemia, and stomach pain associated with laboratory findings (increased CRP, D-dimers, pro BNP, troponins, IL-6), supported by positive contact with SARS-CoV2 one month before the disease onset and increased IgG and IgM anti-SARS-CoV2 antibodies. From the second day of hospitalization, left-side hemiplegia was observed, and using brain CT and MR, CVD was diagnosed. Together with cardiovascular support, corticosteroids and intravenous immunoglobulin were administered. On the fourth day of hospitalization, diagnosis of cerebral salt wasting syndrome (CSWS) was made according to severe dehydration, polyuria, hyponatremia, increased natriuria, and increased urine: serum osmolality ratio. CSWS had very severe course lasting more than one month. The girl was discharged with stable vital signs, normal diuresis and hemiparesis. Conclusion. This is the first case in the literature presenting association of severe CSWS and CVD in a child with MIS-C after COVID-19.
Introduction. Infantile hemiconvulsion?hemiplegia and epilepsy (IHHE) syndrome is defined as a specific syndrome in patients < 2 years of age, presenting as a new onset refractory status epilepticus ...with unilateral motor seizures and acute imaging abnormalities, fever, hemiparesis > 24 hours, and excluding infectious encephalitis. Case outline. We present the results of a follow-up in a 11-year-old girl with IHHE, associated with GRIN2A mutation. The girl had normal development until the first febrile hemiconvulsive status epilepticus at the age of seven months. Neuroimaging initially showed right hemisphere edema, followed by progressive right side hemiatrophy. The patient has resistant epilepsy, left side hemiparesis, and good language and cognitive development. Conclusion. Despite IHHE described many years ago, some syndrome?s features, including etiology, have remained unexplained. The association between IHHE and GRIN2A mutation stated in the current manuscript is described in scientific literature for the first time.
PDF
