Publications by authors named "Stefano Sartori"

120 Publications

A nationwide study on Sydenham's chorea: Clinical features, treatment and prognostic factors.

Eur J Paediatr Neurol 2021 Nov 6;36:1-6. Epub 2021 Nov 6.

Pediatric Rheumatology, Pediatric University Department, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy.

Objectives: Sydenham's Chorea (SC) is a neuropsychiatric disorder and a major manifestation of acute rheumatic fever. The erroneous assumption that SC is a benign and self-limiting disease, has led to a lack of high-quality scientific evidence of the therapeutical and prognostic features of SC.

Study Design: We retrospectively analyzed the medical records of patients <18-years old with SC in 17 Italian pediatric centers. Recorded data included clinical, instrumental and laboratory parameters. Prognostic risk factors including treatment regimens were assessed with univariate and multivariate sub-analysis.

Results: We included 171 patients with SC. 66% had generalized chorea, and 34% hemichorea. 81% had carditis (subclinical in 65%). Additional neurological symptoms were reported in 60% of the patients, mainly dysarthria and dysgraphia. 51% had neuropsychiatric symptoms at onset, which persisted after 12 months in 10%. Among psychiatric manifestations, the most common was anxiety disorder/depression (77%). Neurological remission was reached by 93% of the patients at 6 months; 9% relapsed. Patients were treated as follows: 11% penicillin alone, 37% immunomodulatory therapy, 16% symptomatic drugs (i.e. anti-seizure medication, dopamine antagonists) and 37% both symptomatic and immunomodulatory treatment. Neurological outcome did not differ between groups. Patients receiving symptomatic drugs had a higher risk of relapse on multivariate analysis (p = 0.045).

Conclusions: Treatment of SC was largely heterogeneous. Based on our results, immunomodulatory therapy did not show higher efficacy at medium term, although it was associated to a slightly lower risk of relapse compared to symptomatic therapy. Longitudinal studies are needed to assess specific risk factors and best treatment options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2021.11.002DOI Listing
November 2021

Use and Safety of Immunotherapeutic Management of N-Methyl-d-Aspartate Receptor Antibody Encephalitis: A Meta-analysis.

JAMA Neurol 2021 Nov;78(11):1333-1344

Children's National Medical Center, Washington, DC.

Importance: Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear.

Objective: To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score.

Data Sources: Systematic search in PubMed from inception to January 1, 2019.

Study Selection: Published articles including patients with NMDARE with positive NMDAR antibodies and available individual immunotherapy data.

Data Extraction And Synthesis: Individual patient data on immunotherapies, clinical characteristics at presentation, disease course, and final functional outcome (modified Rankin Scale [mRS] score) were entered into multivariable logistic regression models.

Main Outcomes And Measures: The planned study outcomes were functional outcome at 12 months from disease onset (good, mRS score of 0 to 2; poor, mRS score greater than 2) and monophasic course (absence of relapse at 24 months or later from onset).

Results: Data from 1550 patients from 652 articles were evaluated. Of these, 1105 of 1508 (73.3%) were female and 707 of 1526 (46.3%) were 18 years or younger at disease onset. Factors at first event that were significantly associated with good functional outcome included adolescent age and first-line treatment with therapeutic apheresis, corticosteroids plus intravenous immunoglobulin (IVIG), or corticosteroids plus IVIG plus therapeutic apheresis. Factors significantly associated with poor functional outcome were age younger than 2 years or age of 65 years or older at onset, intensive care unit admission, extreme delta brush pattern on electroencephalography, lack of immunotherapy within the first 30 days of onset, and maintenance IVIG use for 6 months or more. Factors significantly associated with nonrelapsing disease were rituximab use or maintenance IVIG use for 6 months or more. Adolescent age at onset was significantly associated with relapsing disease. Rituximab use increased from 13.5% (52 of 384; 2007 to 2013) to 28.3% (311 of 1100; 2013 to 2019) (P < .001), concurrent with a falling relapse rate over the same period (22% [12 of 55] in 2008 and earlier; 10.9% [35 of 322] in 2017 and later; P = .006). Modified NEOS score (including 4 of 5 original NEOS items) was associated with probability of poor functional status at 1 year (20.1% [40 of 199] for a score of 0 to 1 points; 43.8% [77 of 176] for a score of 3 to 4 points; P = .05).

Conclusions And Relevance: Factors influencing functional outcomes and relapse are different and need to be considered independently in development of evidence-based optimal management guidelines of patients with NMDARE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2021.3188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453367PMC
November 2021

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications.

Brain 2021 Aug 25. Epub 2021 Aug 25.

National Centre for Rare Epilepsy-Related Disorders, Oslo University Hospital, 0001 Oslo, Norway.

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel NaV1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups could be identified: 1) Benign familial infantile epilepsy (BFIE) (n = 15, normal cognition, treatable seizures), 2) intermediate epilepsy (n = 33, mild ID, partially pharmaco-responsive), 3) developmental and epileptic encephalopathy (DEE, n = 177, severe ID, majority pharmaco-resistant), 4) generalized epilepsy (n = 20, mild to moderate ID, frequently with absence seizures), 5) unclassifiable epilepsy (n = 127), and 6) neurodevelopmental disorder without epilepsy (n = 20, mild to moderate ID). Groups 1-3 presented with focal or multifocal seizures (median age of onset: four months) and focal epileptiform discharges, whereas the onset of seizures in group 4 was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human NaV1.6 channels and whole-cell patch-clamping. Two variants causing DEE showed a strong gain-of-function (GOF, hyperpolarising shift of steady-state activation, strongly increased neuronal firing rate), and one variant causing BFIE or intermediate epilepsy showed a mild GOF (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (LOF, reduced current amplitudes, depolarising shift of steady-state activation, reduced neuronal firing). Including previous studies, functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested GOF variant had either focal (97, groups 1-3), or unclassifiable epilepsy (39), whereas 34 with a LOF variant had either generalized (14), no (11) or unclassifiable (6) epilepsy; only three had DEE. Computational modeling in the GOF group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. GOF variant carriers responded significantly better to sodium channel blockers (SCBs) than to other anti-seizure medications, and the same applied for all individuals of groups 1-3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of LOF variant carriers and the extent of the electrophysiological dysfunction of the GOF variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that SCBs present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awab321DOI Listing
August 2021

Efficacy of lacosamide in neonatal-onset super-refractory status epilepticus: a case report.

Epileptic Disord 2021 Aug;23(4):655-660

Paediatric Neurology and Neurophysiology Unit, Department of Woman's and Child's Health, Padova University Hospital, Padova, Italy.

We report the case of a previously healthy newborn who developed super-refractory status epilepticus after Group B streptococcal meningoencephalitis. After administration of first-, second- and third-line anticonvulsants without resolution of status epilepticus, we started intravenous lacosamide as adjunctive therapy to phenobarbital, phenytoin and continuous infusion of ketamine and midazolam. After administration of lacosamide, we observed a clear-cut improvement in the neurological clinical condition coupled with seizure control on continuous video-EEG monitoring, even after suspension of all other medications except for phenobarbital. No adverse effects ascribable to lacosamide were reported. The available data regarding the use of lacosamide for status epilepticus in adults and children are promising, although there is as yet only anecdotal evidence for neonatal status epilepticus. Its lack of potential interactions, good tolerability and the option of intravenous use lend to its appeal as treatment for status epilepticus. To the best of our knowledge, this is one of the first reported cases of effective lacosamide infusion in neonatal-onset super-refractory status epilepticus. This evidence should prompt further investigation on efficacy and safety of lacosamide to support its use in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2021.1307DOI Listing
August 2021

Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis.

Neuroimage 2021 10 18;239:118281. Epub 2021 Jun 18.

Department of Neuropediatrics, University Children's Hospital Zurich, University of Zurich, 8032, Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, University of Zurich, 8032, Zurich, Switzerland. Electronic address:

Plasticity of synaptic strength and density is a vital mechanism enabling memory consolidation, learning, and neurodevelopment. It is strongly dependent on the intact function of N-Methyl-d-Aspartate Receptors (NMDAR). The importance of NMDAR is further evident as their dysfunction is involved in many diseases such as schizophrenia, Alzheimer's disease, neurodevelopmental disorders, and epilepsies. Synaptic plasticity is thought to be reflected by changes of sleep slow wave slopes across the night, namely higher slopes after wakefulness at the beginning of sleep than after a night of sleep. Hence, a functional NMDAR deficiency should theoretically lead to altered overnight changes of slow wave slopes. Here we investigated whether pediatric patients with anti-NMDAR encephalitis, being a very rare but unique human model of NMDAR deficiency due to autoantibodies against receptor subunits, indeed show alterations in this sleep EEG marker for synaptic plasticity. We retrospectively analyzed 12 whole-night EEGs of 9 patients (age 4.3-20.8 years, 7 females) and compared them to a control group of 45 healthy individuals with the same age distribution. Slow wave slopes were calculated for the first and last hour of Non-Rapid Eye Movement (NREM) sleep (factor 'hour') for patients and controls (factor 'group'). There was a significant interaction between 'hour' and 'group' (p = 0.013), with patients showing a smaller overnight decrease of slow wave slopes than controls. Moreover, we found smaller slopes during the first hour in patients (p = 0.022), whereas there was no group difference during the last hour of NREM sleep (p = 0.980). Importantly, the distribution of sleep stages was not different between the groups, and in our main analyses of patients without severe disturbance of sleep architecture, neither was the incidence of slow waves. These possible confounders could therefore not account for the differences in the slow wave slope values, which we also saw in the analysis of the whole sample of EEGs. These results suggest that quantitative EEG analysis of slow wave characteristics may reveal impaired synaptic plasticity in patients with anti-NMDAR encephalitis, a human model of functional NMDAR deficiency. Thus, in the future, the changes of sleep slow wave slopes may contribute to the development of electrophysiological biomarkers of functional NMDAR deficiency and synaptic plasticity in general.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2021.118281DOI Listing
October 2021

Epidemiology of neuronal surface antibody-mediated autoimmune encephalitis and antibody-based diagnostics.

J Neuroimmunol 2021 08 1;357:577598. Epub 2021 May 1.

Department of Neurology, Ospedale Santa Chiara, Trento, Italy.

Epidemiologic data on neuronal surface antibody (NSAb)-associated autoimmune encephalitides (NSAE) are scarce and heterogeneous. We review our 13-year-long biobank-data collection and provide the incidence of NSAE in two Italian provinces (approx. Population of 1,400,000) over a 5-year period (July 2013-June 2018). NSAbs were diagnosed in 75 out of 1179 tested patients (6.4%). The most common NSAbs were anti-LGI1 (30 cases), followed by NMDAR (24). Eleven cases of NSAE were diagnosed in Treviso and Trento provinces with an estimated incidence of 1.54 per 1,000,000 population (LGI1-encephalitis 0.84; C.I. 0.38-1.88). LGI1-E is the most frequent NSAE among adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneuroim.2021.577598DOI Listing
August 2021

Refining the mutational spectrum and gene-phenotype correlates in pontocerebellar hypoplasia: results of a multicentric study.

J Med Genet 2021 Mar 5. Epub 2021 Mar 5.

Unit of Neuromuscular and Neurodegenerative Diseases, Department of Neuroscience and Neurorehabilitation, IRCCS Bambino Gesù Children's Hospital, Roma, Italy.

Background: Pontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.

Methods: We performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.

Results: A genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was , which accounted for nearly half cases (45%) and was mutated in females and occasionally in males. The European founder mutation p.Ala307Ser in and pathogenic variants in accounted for 18% and 9% of cases, respectively. , and were mutated in single patients. We were able to confirm only few previously reported associations, including jitteriness and clonus with and lower motor neuron signs with . When considering multiple features simultaneously, a clear association with a phenotypic cluster only emerged for .

Conclusion: represents the major PCH causative gene in Italy. Phenotypic variability associated with the most common genetic causes of PCH is wider than previously thought, with marked overlap between and -associated disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jmedgenet-2020-107497DOI Listing
March 2021

Isolated Third Cranial Nerve Palsy and COVID-19 Infection in a Child.

Pediatr Neurol 2021 07 2;120:11. Epub 2021 Apr 2.

Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy; Neuroimmunology Group, Paediatric Research Institute Città della Speranza, Padua, Italy; Department of Neurosciences (DNS), University of Padua, Padua, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2021.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016536PMC
July 2021

Quantification of 17 Endogenous and Exogenous Steroidal Hormones in Equine and Bovine Blood for Doping Control with UHPLC-MS/MS.

Pharmaceuticals (Basel) 2021 Apr 21;14(5). Epub 2021 Apr 21.

School of Pharmacy, University of Camerino, 62032 Camerino, Italy.

A simple and fast analytical method able to simultaneously identify and quantify 17 endogenous and exogenous steroidal hormones was developed in bovine and equine blood using UHPLC-MS/MS. A total amount of 500 µL of sample was deproteinized with 500 µL of a mixture of methanol and zinc sulfate and evaporated. The mixture was reconstituted with 50 µL of a solution of 25% methanol and injected in the UHPLC-MS/MS triple quadrupole. The correlation coefficients of the calibration curves of the analyzed compounds were in the range of 0.9932-0.9999, and the limits of detection and quantification were in the range of 0.023-1.833 and 0.069-5.5 ppb, respectively. The developed method showed a high sensitivity and qualitative aspects allowing the detection and quantification of all steroids in equine and bovine blood. Moreover, the detection limit of testosterone (50 ppt) is half of the threshold admitted in plasma (100 ppt). Once validated, the method was used to quantify 17 steroid hormones in both bovine and equine blood samples. The primary endogenous compounds detected were corticosterone (range 0.28-0.60 ppb) and cortisol (range 0.44-10.00 ppb), followed by androstenedione, testosterone and 11-deoxycortisol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ph14050393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143330PMC
April 2021

Identification of Mutations by Gene Panel Sequencing in Individuals With Intellectual Disability or With "Developmental and Epileptic Encephalopathy".

Front Neurol 2020 16;11:593446. Epub 2020 Dec 16.

Molecular Genetics of Neurodevelopment, Department of Woman and Child Health, University of Padova, Padua, Italy.

mutations are associated with the Schinzel-Giedion syndrome (SGS), characterized by profound neurodevelopmental delay, typical facial features, and multiple congenital malformations (OMIM 269150). Refractory epilepsy is a common feature of SGS. Loss of function mutations have been typically associated with a distinct and milder phenotype characterized by intellectual disability and expressive speech impairment. Here we report three variants of , two novel truncating mutations, identified by NGS analysis of an Intellectual Disability gene panel in 600 subjects with non-specific neurodevelopmental disorders, and one missense identified by a developmental epilepsy gene panel tested in 56 pediatric epileptic cases. The three individuals carrying the identified variants presented mild to severe developmental delay and lacked the cardinal features of classical SGS. One of these subjects, carrying the c.1765C>T (p.Arg589) mutation, had mild Intellectual Disability with speech delay; the second one carrying the c.2199_2203del (p.Glu734Alafs19) mutation had generalized epilepsy, responsive to treatment, and moderate Intellectual Disability; the third patient showed a severe cognitive defects and had a history of drug resistant epilepsy with West syndrome evolved into a Lennox-Gastaut syndrome. This latter subject carries the missense c.2572G>A (p.Glu858Lys) variant, which is absent from the control population, reported as in a subject with ASD, and located close to the hot spot for SGS-associated mutations. Our findings contribute to further characterizing the associated phenotypes and suggest inclusion of in the list of prioritized genes for the genetic diagnosis of overlapping phenotypes ranging from non-specific neurodevelopmental disorders to "developmental and epileptic encephalopathy" (DEE).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.593446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772201PMC
December 2020

Sleep Exacerbations and Facial Twitching: Diagnostic Clues for ADCY5-Related Dyskinesias.

Neuropediatrics 2021 06 29;52(3):208-211. Epub 2020 Dec 29.

Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1721685DOI Listing
June 2021

Executive Functions and Attention in Childhood Epilepsies: A Neuropsychological Hallmark of Dysfunction?

J Int Neuropsychol Soc 2021 08 13;27(7):673-685. Epub 2020 Nov 13.

Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padova, 35100Padova, Italy.

Objective: Patients with epilepsy are at risk for several lifetime problems, in which neuropsychological impairments may represent an impacting factor. We evaluated the neuropsychological functions in children suffering from three main epilepsy categories. Further, we analyzed the longitudinal evolution of the neuropsychological profile over time.

Methods: Patients undergoing neuropsychological evaluation at our Department from 2012 to 2018 were identified retrospectively. We selected patients aged 6-16 years and with at least two evaluations. Three epilepsy categories were considered: focal/structural, focal self-limited, and idiopathic generalized. Each evaluation included the same structured assessment of main neuropsychological domains. The effect of the epilepsy category, illness duration, seizure status, and medication was computed in multilevel models.

Results: We identified 103 patients (focal self-limited = 27; focal/structural = 51; and idiopathic generalized = 25), for 233 evaluations. The majority of deficits were reported in attention and executive functions (>30% of patients); the results were dichotomized to obtain global indexes. Multilevel models showed a trend toward statistical significance of category of epilepsy on the global executive index and of illness duration on global attention index. Illness duration predicted the scores of executive and attention tasks, while category and medication predicted executive task performance. Focal/structural epilepsies mostly affected the executive domain, with deficits persisting over time. By contrast, an ameliorative effect of illness duration for attention was documented in all epilepsies.

Conclusions: This study offers lacking information about the evolution of deficits in time, the role of epilepsy category, and possible psychological implications for high-order cognitive skills, central in several social and academic problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1355617720001125DOI Listing
August 2021

Posterior Reversible Encephalopathy Syndrome in infants and young children.

Eur J Paediatr Neurol 2021 Jan 28;30:128-133. Epub 2020 Oct 28.

Unit of Pediatric Oncology and Haematology "Lalla Seràgnoli", Department of Pediatrics, Sant'Orsola Hospital, University of Bologna, Bologna, Italy. Electronic address:

Aim: The aim of this study was to describe the characteristics of Posterior Reversible Encephalopathy Syndrome (PRES) in infants and young children (<6 years) and to compare them with the older pediatric population affected by PRES.

Methods: we retrospectively reviewed records of 111 children (0-17 years) diagnosed with PRES from 2000 to 2018 in 6 referral pediatric hospitals in Italy. The clinical, radiological and EEG features, as well as intensive care unit (ICU) admission rate and outcome of children aged <6 years were compared to those of older children (6-17 years). Factors associated with ICU admission in the whole pediatric cohort with PRES were also evaluated.

Results: Twenty-nine patients younger than 6 years (26%) were enrolled with a median age at onset of PRES of 4 years (range: 6 months-5 years). Epileptic seizures were the most frequent presentation at the disease onset (27/29 patients). Status epilepticus (SE) was observed in 21/29 patients: in detail, 11 developed convulsive SE and 10 presented nonconvulsive SE (NCSE). SE was more frequent in children <6 years compared with older children (72% vs 45%) as well as NCSE (35% vs 10%). Seventeen children aged <6 years required ICU admission. Prevalence of ICU admissions was higher within younger population compared to older (59% vs 37%). In the whole study population SE was significantly associated with ICU admission (p = 0.001).

Conclusions: PRES in children < 6 years differs from older children in clinical presentation suggesting a more severe presentation at younger age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2020.10.009DOI Listing
January 2021

Visual cortex changes in children with sickle cell disease and normal visual acuity: a multimodal magnetic resonance imaging study.

Br J Haematol 2021 01 12;192(1):151-157. Epub 2020 Aug 12.

Department of Child and Woman's Health, Azienda Ospedaliera-Università di Padova, Padova, Italy.

The visual system is primarily affected in sickle cell disease (SCD), and eye examination is recommended starting in late childhood. So far, to our knowledge, all studies have focused on the retina, neglecting the changes that might be present in the cortical portion of the visual system. We performed a multimodal magnetic resonance imaging (MRI) evaluation of the visual cortex in 25 children with SCD (mean age: 12·3 ± 1·9 years) and 31 controls (mean age: 12·7 ± 1·6 years). At ophthalmologic examination, 3/25 SCD children had mild visual acuity deficits and 2/25 had mild tortuosity of the retinal vessels. None showed optic pathway infarcts at MRI or Transcranial Doppler abnormal blood velocities, and 6/25 disclosed posterior cerebral artery stenosis (five mild and one severe) at MR-angiography. Compared to controls, SCD children had increased posterior pericalcarine cortical thickness, with a different trajectory of cortical maturation and decreased connectivity within medial and ventral visual neural networks. Our findings suggest that SCD affects the development and the tuning of the visual cortex, leading to anatomical and functional changes in childhood even in the absence of retinopathy, and set the basis for future studies to determine if these changes can represent useful predictors of visual impairment in adulthood, biomarkers of disease progression or treatment response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17042DOI Listing
January 2021

Toll-like receptor 3 pathway deficiency, herpes simplex encephalitis, and anti-NMDAR encephalitis: more questions than answers.

Pediatr Res 2021 04 17;89(5):1043. Epub 2020 Jun 17.

Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padova, Padova, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41390-020-1018-zDOI Listing
April 2021

Dexmedetomidine for EEG sedation in children with behavioral disorders.

Acta Neurol Scand 2020 Nov 6;142(5):493-500. Epub 2020 Jul 6.

Pediatric Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Padova, Padova, Italy.

Objective: To evaluate the efficacy and safety of sedation with dexmedetomidine, a highly selective α2-agonist with sedative effect, for EEG recording in children with behavioral disorders.

Material And Methods: Prospective observational study on children with behavioral disorders undergoing EEG at the Pediatric Hospital in Padova, Italy. A 2 mcg/kg intravenous bolus of dexmedetomidine was administered, followed by a 1-2 mcg/kg/h infusion. If necessary, bolus was repeated up to 3 times to reach the target level of sedation, assessed by Pediatric Sedation State Scale. Patients were fully monitored before, during and after the procedure until complete recovery. EEG recording quality, and caregivers' satisfaction were collected. Any adverse effect was registered using SIVA score.

Results: For this preliminary study, 19 patients were enrolled. EEG was successfully completed in all of them. Mean total dose of dexmedetomidine was 3.7 ± 1.7 mcg/kg. Adequate sedation was achieved within 11.9 ± 8 minutes. Mean time to first awakening was 30.9 ± 36.9 minutes and time to complete recovery 113.3 ± 92.7 minutes. Adverse effects (hypotension, bradycardia) were reported in 10 patients, all classified as "minor." EEG recording quality was good or excellent. Parents' satisfaction was high in all the interviewed families.

Conclusions: Intravenous dexmedetomidine as a single drug showed an excellent efficacy and good safety profile for EEG recording in children with behavioral disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ane.13293DOI Listing
November 2020

Cardiac Myxoma as a Rare Cause of Pediatric Arterial Ischemic Stroke: Case Report and Literature Review.

Neuropediatrics 2020 12 5;51(6):389-396. Epub 2020 May 5.

Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua, Padova, Italy.

Background: Cardiac disorders are the second leading cause of pediatric arterial ischemic stroke (AIS). Limited literature is available on pediatric AIS caused by cardiac myxoma, a rare tumor in childhood.

Methods: We describe a new case of pediatric AIS due to a previously unknown atrial myxoma and we conduct a literature review on children with AIS due to cardiac myxoma.

Results: We identified 41 published pediatric cases of AIS and cardiac myxoma, including ours (56% males, median age at AIS was 11 years [range: 3-18]). AIS presentation was most frequently with hemiparesis/hemiplegia (89%). Multiple brain ischemic lesions were detected in 69% of patients, and arteriopathy in 91%. Seven patients underwent mechanical thrombectomy. At AIS presentation, 73% of children had one or more of the following clinical symptoms/signs suggesting a possible underlying cardiac myxoma: Carney's complex, cardiac auscultation abnormalities, extraneurological symptoms/signs, such as skin signs (12, 38, and 65%, respectively). Cardiac myxoma was diagnosed within 72 hours in 68% of cases. Death occurred in 11%, and 40% had persistent neurological deficits.

Conclusion: Neurological presentation of AIS due to cardiac myxoma is similar to that of AIS with other etiologies, although clues suggesting a possible underlying cardiac myxoma can be detected in most cases. A timely diagnosis of cardiac myxoma in patients with AIS may favor prompt identification of candidates for endovascular therapy. Therefore, we suggest that in otherwise-healthy children presenting with AIS, transthoracic echocardiography should be performed early after stroke presentation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1710338DOI Listing
December 2020

High association of MOG-IgG antibodies in children with bilateral optic neuritis.

Eur J Paediatr Neurol 2020 Jul 15;27:86-93. Epub 2020 Apr 15.

Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Germany. Electronic address:

Background: Bilateral optic neuritis (bilON) is a rare clinical presentation often thought to be associated with relapsing disorders such as neuromyelitis optica spectrum disorders (NMOSD) or multiple sclerosis (MS).

Objective: To characterize the clinical, radiological phenotype and antibody status of children presenting with bilON.

Material And Methods: Retrospective multicenter study on children with bilON age <18 years with a first episode aquired demyelinating syndrome (ADS), cMRI, AQP4- and serum MOG-antibody status and follow-up data were collected.

Results: 30 patients (f:m = 15:15, median age 8.0y) with bilON met the inclusion criteria. 22/30 (73%) were MOG-positive (median: 1:1280, range: 1:160-1:1520). No patient showed AQP4-abs. 4/30 patients (13%), all with high MOG-abs titers, had recurrent episodes. No patient developed MS. Improvement after IVMP was observed in most patients (26/30; 87%). Outcome was favorable with no sequelae in 22/30 patients. Serial MOG-abs titers tested in 15/22 patients decreased to a median of 1:160 (range: 0-1:640) over a period of 31 months (range: 2-141 months) in 14/15 (93%) patients. MR imaging showed a predominantly anterior affection of the visual system in seropositive patients with bilateral intraorbital lesions in 68% (15/22), compared to 25% in MOG-negative patients (2/8).

Conclusion: Pediatric bilON is associated with high MOG-abs titers in combination with anterior involvement of the visual system. Despite severe loss of vision, the majority of patients shows distinct recovery after IVMP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2020.04.002DOI Listing
July 2020

Reply to Dr. Capovilla on "Reply to the article "Management of status epilepticus in adults. Position paper of the Italian League Against Epilepsy"".

Epilepsy Behav 2020 06 6;107:107048. Epub 2020 Apr 6.

IRCCS Istituto delle Scienze Neurologiche, Bellaria Hospital, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2020.107048DOI Listing
June 2020

Possible clinical role of MOG antibody testing in children presenting with acute neurological symptoms.

Neurol Sci 2020 Sep 3;41(9):2553-2559. Epub 2020 Apr 3.

Department of Laboratory Medicine, University-Hospital of Padova, via Giustiniani 2, 35128, Padova, Italy.

The differential diagnosis between acquired inflammatory demyelinating syndromes of the central nervous system (CNS), such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and acute disseminated encephalomyelitis (ADEM) can be very challenging at onset. Apart from cerebrospinal fluid oligoclonal bands and anti-aquaporin-4 antibodies (AQP4-Ab), definite diagnostic biomarkers are lacking. Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) have been increasingly described in children with AQP4-seronegative NMOSD, ADEM and other inflammatory demyelinating CND syndromes; despite partial overlaps with AQP4-Ab disease, a novel "MOG-Ab-disorder" phenotype has been suggested. In this study, we tested the presence of MOG-Ab and AQP4-Ab in 57 children at first onset of acute neurological symptoms; three clinical subgroups were identified: 12 patients had acquired inflammatory demyelinating CNS syndromes, 11 had other autoimmune/immune-mediated disorders of the central and peripheral nervous system and 34 had non-immune-mediated CNS disorders. MOG-Abs were found positive only in a subset of cases in the subgroup with acquired inflammatory demyelinating CNS syndromes (in 2/12 patients, both with non-MS phenotype) and in none of the patients with other autoimmune and immune-mediated disorders of the central and peripheral nervous system or with non-immune-mediated disorders of the CNS.Data from the literature review support clinical and analytical observations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-020-04379-5DOI Listing
September 2020

A Novel WAC Loss of Function Mutation in an Individual Presenting with Encephalopathy Related to Status Epilepticus during Sleep (ESES).

Genes (Basel) 2020 03 24;11(3). Epub 2020 Mar 24.

Molecular Genetics of Neurodevelopment, Department of Women's and Children's Health, University of Padova, 35128 Padova, Italy.

WAC (WW Domain Containing Adaptor With Coiled-Coil) mutations have been reported in only 20 individuals presenting a neurodevelopmental disorder characterized by intellectual disability, neonatal hypotonia, behavioral problems, and mildly dysmorphic features. Using targeted deep sequencing, we screened a cohort of 630 individuals with variable degrees of intellectual disability and identified five rare variants: two variants were inherited from healthy parents; two previously reported de novo mutations, c.1661_1664del (p.Ser554*) and c.374C>A (p.Ser125*); and a novel c.381+2T>C variant causing the skipping of exon 4 of the gene, inherited from a reportedly asymptomatic father with somatic mosaicism. A phenotypic evaluation of this individual evidenced areas of cognitive and behavioral deficits. The patient carrying the novel splicing mutation had a clinical history of encephalopathy related to status epilepticus during slow sleep (ESES), recently reported in another individual. This first report of a somatic mosaic remarks the contribution of mosaicism in the etiology of neurodevelopmental and neuropsychiatric disorders. We summarized the clinical data of reported individuals with pathogenic mutations, which together with our findings, allowed for the expansion of the phenotypic spectrum of WAC-related disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes11030344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141116PMC
March 2020

Cerebellar gray matter lesions are common in pediatric multiple sclerosis at clinical onset.

J Neurol 2020 Jun 5;267(6):1824-1829. Epub 2020 Mar 5.

Multiple Sclerosis Centre of the Veneto Region (CeSMuV), University Hospital of Padua, Via Giustiniani 2, 35128, Padua, Italy.

Background: No data are available on the occurrence of gray matter lesions (GML) in the cerebellum of pediatric multiple sclerosis (pedMS).

Objectives: We analyzed frequency, number and topography of GML, and their correlation with cerebellar-related disability in pedMS at clinical onset.

Methods: Fifteen adolescents with pedMS (12F/3M; mean age 14.9 ± 2.2, range 11-17) were studied. Neurological and cognitive evaluations were done by means of EDSS, Trail Making Test-Part B (TMT-B) and Symbol Digit Modalities Test-oral version (SDMT). Cerebellar GML were investigated with double inversion recovery (DIR) and phase-sensitive inversion recovery (PSIR) sequences obtained with a 3 T-MRI scan.

Results: All patients had white matter lesions (WML) and/or GML in the cerebellum. A significantly higher GML number was observed on PSIR compared to DIR (mean 2.3 ± 2.3 vs 1.1 ± 1.6; median 2.0 (IQR 1.0-2.0) vs 1.0 (IQR 0.0-1.5); p = 0.004). GML were observed in 14/15 (93.3%) patients and were more frequent in the posterior than in the anterior lobe (mean 1.8 ± 2.2 vs 0.47 ± 0.74; median 2.0 (IQR 0.5-2.0) vs 0.0 (IQR 0.0-1.0); p = 0.044). No correlation was found between lesion number or topography and EDSS (r = 0.12, p = 0.69), TMT-B and SDMT.

Conclusion: At clinical onset, cerebellar GML are common in pedMS, are very often asymptomatic, do not correlate with physical and cognitive disability, and more frequently affect the posterior lobe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00415-020-09776-6DOI Listing
June 2020

Pediatric optic neuritis and anti MOG antibodies: a cohort of Italian patients.

Mult Scler Relat Disord 2019 Dec 24;39:101917. Epub 2019 Dec 24.

Unit of Child Neuropsychiatry, Clinical and Surgical Neurosciences Department, IRCCS Istituto Giannina Gaslini, Genova, Italy. Electronic address:

Background: recent studies reported that anti myelin oligodendrocyte glycoprotein (MOG) antibody (ab) related optic neuritis (ON) tend to have characteristics that differ from seronegative ones. The aim of our study was to investigate the clinical characteristics of pediatric anti-MOG ON by comparing anti MOG-ab-seropositive and seronegative patients with ON.

Methods: in this retrospective Italian multicentre study, participants were identified by chart review of patients evaluated for acquired demyelinating syndromes of the central nervous system (over the period 2009-2019). We selected patients presenting with ON as their first demyelinating event. Inclusion criteria were age < 18 years at symptoms onset; presentation consistent with ON; negativity of anti-aquaporin 4 antibodies (AQP4). Only patients who were tested for MOG-IgG1-ab with a live cell-based assay were included.

Results: 22 patients (10 MOG-ab-positive and 12 MOG-ab-negative) were included. Fundus oculi examination at onset showed disc swelling in 9/10 in the MOG-ab-positive cohort and 2/10 in the seronegative group (P = 0.002). Retinal Fiber Nerve Layer (RFNL) thickness measured by Spectral Domain Optical Coherence Tomography (S-OCT) was increased in the 5/5 MOG-ab-positive patients tested and was normal or reduced in the seronegative patients tested (4/4 patients) (P = 0.024). Visual acuity impairment at onset did not differ significantly between the two groups, but the MOG-ab-positive cohort showed better recovery at follow-up both regarding visual acuity (P = 0.025) and expanded disability status scale (EDSS) (P = 0.013). A final diagnosis of MS was frequent among seronegative patients (6/12, 50%), whereas none of the MOG-ab-positive group received a diagnosis of MS (P = 0.015). Clinical relapse frequency was low in both groups: 2/10 MOG-ab-positive and 2/12 seronegative cases relapsed, with a median follow up of 25 months.

Conclusion: optic disc swelling and increased RFNL at baseline are strongly associated with MOG-ab positivity. MOG-ab-positive patients with ON showed better recovery compared to the seronegative ones. The relapse rate was low and did not differ among the two groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2019.101917DOI Listing
December 2019

Management of status epilepticus in adults. Position paper of the Italian League against Epilepsy.

Epilepsy Behav 2020 01 22;102:106675. Epub 2019 Nov 22.

IRCCS Istituto delle Scienze Neurologiche, Bellaria Hospital, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy. Electronic address:

Since the publication of the Italian League Against Epilepsy guidelines for the treatment of status epilepticus in 2006, advances in the field have ushered in improvements in the therapeutic arsenal. The present position paper provides neurologists, epileptologists, neurointensive care specialists, and emergency physicians with updated recommendations for the treatment of adult patients with status epilepticus. The aim is to standardize treatment recommendations in the care of this patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2019.106675DOI Listing
January 2020

First Attack and Clinical Presentation of Hemiplegic Migraine in Pediatric Age: A Multicenter Retrospective Study and Literature Review.

Front Neurol 2019 15;10:1079. Epub 2019 Oct 15.

Department of Woman's and Child's Health, Juvenile Headache Centre, University Hospital of Padua, Padua, Italy.

Data on clinical presentation of Hemiplegic Migraine (HM) are quite limited in the literature, particularly in the pediatric age. The aim of the present study is to describe in detail the phenotypic features at onset and during the first years of disease of sporadic (SHM) and familial (FHM) pediatric hemiplegic migraine and to review the pertinent literature. Retrospective study of a cohort of children and adolescents diagnosed with hemiplegic migraine, recruited from 11 Italian specialized Juvenile Headache Centers. Forty-six cases (24 females) were collected and divided in two subgroups: 32 SHM (16 females), 14 FHM (8 females). Mean age at onset was 10.5 ± 3.8 y (range: 2-16 y). Mean duration of motor aura was 3.5 h (range: 5 min-48 h). SHM cases experienced more prolonged attacks than FHM cases, with significantly longer duration of both motor aura and of total HM attack. Sensory (65%) and basilar-type auras (63%) were frequently associated to the motor aura, without significant differences between SHM and FHM. At follow-up (mean duration 4.4 years) the mean frequency of attacks was 2.2 per year in the first year after disease onset, higher in FHM than in SHM cases (3.9 vs. 1.5 per year, respectively). A literature review retrieved seven studies, all but one were based on mixed adults and children cohorts. This study represents the first Italian pediatric series of HM ever reported, including both FHM and SHM patients. Our cohort highlights that in the pediatric HM has an heterogeneous clinical onset. Children present fewer non-motor auras as compared to adults and in some cases the first attack is preceded by transient neurological signs and symptoms in early childhood. In SHM cases, attacks were less frequent but more severe and prolonged, while FHM patients had less intense but more frequent attacks and a longer phase of active disease. Differently from previous studies, the majority of our cases, even with early onset and severe attacks, had a favorable clinical evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2019.01079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803542PMC
October 2019

Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders.

Nat Commun 2019 10 15;10(1):4679. Epub 2019 Oct 15.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA.

Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2-whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-12435-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794285PMC
October 2019

Photosensitive epilepsy and long QT: expanding Timothy syndrome phenotype.

Clin Neurophysiol 2019 11 17;130(11):2134-2136. Epub 2019 Sep 17.

Department of Woman's and Child's Health, University Hospital of Padua, via Giustiniani, 3 - 35128 Padua, Italy. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2019.09.003DOI Listing
November 2019

LGI1 and CASPR2 autoimmunity in children: Systematic literature review and report of a young girl with Morvan syndrome.

J Neuroimmunol 2019 10 18;335:577008. Epub 2019 Jul 18.

Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua, Italy; Neuroimmunology Group, Paediatric Research Institute "Città della Speranza", Padova, Italy.

Leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) neurological autoimmunity in adults has been associated with various clinical syndromes involving central, peripheral and autonomic nervous system, while data in children is limited. We perform the first systematic literature review on paediatric LGI1 and CASPR2 autoimmunity, with focus on clinical data, in order to contribute to the definition of clinical features of LGI1 and CASPR2 autoimmunity in paediatric age and favour early diagnosis. Additionally, we report the youngest-to-date case of Morvan syndrome. We identified 37 published paediatric cases of LGI1 and/or CASPR2 autoimmunity. Most frequent syndromes were encephalitis in LGI1-positive and isolated epilepsy in CASPR2-positive children, while syndromes with predominant peripheral symptoms were most frequent in double-positive children. With the limitations imposed by the low number of cases, differences to published adult cohorts included: absence of faciobrachial dystonic seizures and hyponatremia in patients with LGI1-positive encephalitis; slightly higher proportion of isolated epilepsy syndromes in CASPR2-positive patients; absence of tumour in the whole cohort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneuroim.2019.577008DOI Listing
October 2019
-->