Reply to Özdemir, Ö. Allergic Disease with Selective IgA Deficiency. Comment on "Cinicola et al. The Allergic Phenotype of Children and Adolescents with Selective IgA Deficiency: A Longitudinal Monocentric Study. J. Clin. Med. 2022, 11, 5705".

We carefully read the correspondence [...].

Peripheral nervous system involvement in SARS-CoV-2 infection: a review of the current pediatric literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the pathogen responsible for the pandemic health emergency declared by the World Health Organization in March 2020. During the first part of the pandemic, adults showed mild to severe respiratory symptoms. Children seemed initially exempt, both from acute and subsequent complications. Hyposmia or anosmia were promptly identified as the main symptoms of acute infection, so neurotropism of SARS-CoV-2 was immediately suspected. (1, 2). As the emergency progressed, post infectious neurological complications were described also in pediatric population (3). Cases of cranial neuropathy in connection with acute SARS-CoV-2 infection have been reported in pediatric patients, as an isolate post infectious complication or in the context of the multisystem inflammatory syndrome in children (MIS-C) (4-6). Neuroinflammation is thought to be caused by several mechanisms, among which immune/autoimmune reactions (7), but so far, no specific autoantibody has been identified. SARS-CoV-2 can enter the central nervous system (CNS) directly and/or infect it retrogradely, through the peripheral nervous system (PNS), after replicating peripherally; several factors regulate invasion and subsequent neuroinflammation. Indeed, direct/secondary entry and replication can activate CNS-resident immune cells that, together with peripheral leukocytes, induce an immune response and promote neuroinflammation. In addition, as we will discuss in the following review, many cases of peripheral neuropathy (cranial and non-cranial) have been reported during or after SARS-CoV-2 infection. However, some authors have pointed out that the increase of cranial roots and ganglia in neurological imaging is not always observed in children with cranial neuropathy. (8). Even if a variety of case reports were published, opinions about an increased incidence of such neurologic diseases, linked to SARS-CoV-2 infection, are still controversial (9-11). Facial nerve palsy, ocular movements abnormalities and vestibular alterations are among the most reported issues in pediatric population (3-5). Moreover, an increased screen exposure imposed by social distancing led to acute oculomotion's disturbance in children, not primarily caused by neuritis (12, 13). The aim of this review is to suggest food for thought on the role of SARS-CoV-2 in neurological conditions, affecting the peripheral nervous system to optimize the management and care of pediatric patients.

Immunological characterization of an Italian PANDAS cohort.

This cross-sectional study aimed to contribute to the definition of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) pathophysiology. An extensive immunological assessment has been conducted to investigate both immune defects, potentially leading to recurrent Group A ß-hemolytic Streptococcus (GABHS) infections, and immune dysregulation responsible for a systemic inflammatory state. Twenty-six PANDAS patients with relapsing-remitting course of disease and 11 controls with recurrent pharyngotonsillitis were enrolled. Each subject underwent a detailed phenotypic and immunological assessment including cytokine profile. A possible correlation of immunological parameters with clinical-anamnestic data was analyzed. No inborn errors of immunity were detected in either group, using first level immunological assessments. However, a trend toward higher TNF-alpha and IL-17 levels, and lower C3 levels, was detected in the PANDAS patients compared to the control group. Maternal autoimmune diseases were described in 53.3% of PANDAS patients and neuropsychiatric symptoms other than OCD and tics were detected in 76.9% patients. ASO titer did not differ significantly between the two groups. A possible correlation between enduring inflammation (elevated serum TNF-α and IL-17) and the persistence of neuropsychiatric symptoms in PANDAS patients beyond infectious episodes needs to be addressed. Further studies with larger cohorts would be pivotal to better define the role of TNF-α and IL-17 in PANDAS pathophysiology.

The Allergic Phenotype of Children and Adolescents with Selective IgA Deficiency: A Longitudinal Monocentric Study.

BACKGROUND: Selective IgA deficiency (SIgAD) is the most common inborn error of immunity. The exact prevalence and pathogenesis of allergy in SIgAD have not yet been defined. We aimed to describe the prevalence and the characteristics of allergy in pediatric SIgAD subjects, evaluate the association between allergy and other comorbidities, and define the immune phenotype of allergic and non-allergic patients. METHODS: Clinical and immunological data from 67 SIgAD patients were collected over a 13-year period at a single center. Patients' characteristics were analyzed according to the presence of allergy. RESULTS: Allergy was diagnosed in 34% of SIgAD patients, with a median age at allergy diagnosis of 8 years. Allergy was the second-most-common clinical manifestation, following recurrent respiratory infections. Among the allergic group, 74% had rhinitis, 30% asthma, 30% atopic dermatitis, and 22% food allergy; one out of three had more than one allergic manifestation. SIgAD patients showed more frequent transitory lymphopenia and a lower count of CD19+ at diagnosis than at last FU. However, compared to non-allergic subjects, allergic patients did not differ in their immune phenotype, number and severity of infections, or increased autoimmunity. CONCLUSIONS: In our longitudinal study, compared to non-allergic SIgAD patients, those with allergies did not present a more severe immune defect or complex clinical phenotype. However, evaluation and early identification of allergy in the context of SIgAD assessment, both at diagnosis and during FU, and definition of a proper management are important to prevent complications and improve the patient's quality of life.

Neurological and psychological effects of long COVID in a young population: A cross-sectional study.

Aim: We evaluated the long-term clinical status of pediatric patients after testing positive for COVID-19. We hypothesized that there are similar symptoms to those that have been described in adults and children and that pediatric patients with neurophysiologic symptoms still present 3-5 months after infection have psychological consequences that interfere with their adaptive functioning. Method: We recruited 322 COVID-19-positive pediatric patients, between 1.5 and 17 years old, from the outpatient clinic for COVID-19 follow-up. Neurological symptoms were analyzed at onset, after 1 month, and after 3-5 months. A psychological assessment with standardized questionnaires was also conducted to determine the impact of the disease. Results: At the onset of COVID-19, 60% of the total sample exhibited symptoms; this decreased after 1 month (20%) but stabilized 3-5 months after disease onset (22%). Prevailing long-COVID neurological symptoms were headache, fatigue, and anosmia. In the 1.5-5-year-old subgroup, internalizing problems emerged in 12% of patients. In the 6-18-year-old subgroup, anxiety and post-traumatic stress showed significant associations with neurological symptoms of long COVID. Conclusions: These data demonstrate that long COVID presents various broad-spectrum symptoms, including psychological and long-lasting cognitive issues. If not treated, these symptoms could significantly compromise the quality of life of children and adolescents.

COVID-19, Anosmia, and Allergies: Is There a Relationship? A Pediatric Perspective.

BACKGROUND: Between June and July 2020, we evaluated children and adolescents concerning post-infection surveillance after a COVID-19 positivity during the lockdown. We aimed to assess whether the anamnestic presence of allergies could correlate with the presence of SARS-CoV-2 symptoms, and in particular with anosmia. MATERIAL AND METHODS: For each patient, we collected anamnestic data, the presence of allergies documented by performing skin prick tests, and COVID-19 symptoms. Then, if over six years of age, each patient underwent an active anterior rhinomanometry. RESULTS: A total of 296 patients were enrolled, of whom 105 (35.4%) reported allergies. Considering COVID-19 symptoms, 74 subjects (25%) presented an asymptomatic form, 222 (75%) reported symptoms, and anosmia recurred in 60 subjects (27.03%). A statistically significant relationship was found between allergies and symptomatic COVID-19 (p = 0.042), allergies, and anosmia (p = 0.05), and allergies and anosmia in males (p = 0.007). Moreover, anosmic patients presented a higher body mass index, older age, and a longer COVID-19 duration with statistical significance (p = 0.001, 0.001, 0.006, respectively). CONCLUSIONS: Allergic subjects seem to develop symptomatic COVID-19 more frequently and allergies appear to be a protective factor from anosmia's onset in males.

Short-Term Side Effects and SARS-CoV-2 Infection after COVID-19 Pfizer-BioNTech Vaccine in Children Aged 5-11 Years: An Italian Real-World Study.

Vaccination against COVID-19 is the most effective tool to protect both the individual and the community from this potentially life-threatening infectious disease. Data from phase-3 trials showed that two doses of the BNT162b2 vaccine were safe, immunogenic, and effective against COVID-19 in children aged 5-11 years. However, no surveys in real-life settings have been carried out in this age range. Here, we conducted a cross-sectional study to evaluate the short-term adverse reactions (ARs) and the rate of protection against infection of the BNT162b2 vaccine in children aged 5-11 years by the compilation of two surveillance questionnaires conceived using Google Forms. Five-hundred and ninety one children were included in the analysis. ARs were reported by 68.9% of the children, being mainly local. The incidence of systemic ARs, especially fever, was higher after the second dose. The incidence of infection after completing the immunization accounted for 13.6% of the children. COVID-19 symptoms reported were mild, with the exception of one case of pneumonia. Only 40% of infected participants needed to take medication to relieve symptoms, mostly paracetamol and NSAIDs, and none reported persistent symptoms. The Pfizer-BioNTech vaccine in children aged 5-11 years is safe and well tolerated. The mild clinical course of COVID-19 in immunized children confirmed the favorable risk-benefit ratio, encouraging parents to immunize their children.

COVID-19 and abducens nerve palsy in a 9-year-old girl-case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although many reports have detailed a range of neurological symptoms in SARS-CoV-2-infected patients, studies of neuro-ophthalmological manifestations are still scarce. CASE PRESENTATION: We report a 9-year-old girl with abducens nerve palsy after COVID-19 with no evidence of other neurological disease on neuroimaging. At 2-month follow-up clinical conditions were improved. CONCLUSIONS: The palsy may have occurred due to a possible post-infectious immune-mediated mechanism underlying the neuropathy, as opposed to direct viral infiltration. Despite being rare, this complication must be taken into account.

Physical and Neurological Development of a Girl Born to a Mother with Methylmalonic Acidemia and Kidney Transplantation and Review of the Literature.

BACKGROUND: actual literature suggests that children of methylmalonic acidemia patients are mostly healthy, but data are only partial, especially regarding long-term outcome. Therefore, our aim was to evaluate the possible long-term neurological effects of fetal exposure to high levels of methylmalonic acid in a child of a renal transplant recipient. METHODS: we retrospectively evaluated the clinical and neurological records of a girl whose mother is a kidney transplant recipient affected by methylmalonic acidemia. Subsequently, we compared our results with the ones already published. RESULTS: the girl's weight and stature were within the normal range in the first years of life but, starting from 4 years of age, she became progressively overweight. Regarding the neurodevelopment aspects, for the first time we performed a complete and seriated neuropsychological evaluation, highlighting a mild but significant weakness in the verbal domain, with a worsening trend at three-year revaluation. CONCLUSIONS: since children of MMA patients are exposed to methylmalonic acid, the efforts of the physicians caring for these children should be directed on careful evaluation of growth, prevention of obesity and regular neurological examination together with structured neuropsychological tests to achieve a better insight in possible complications of pregnancy in patients suffering from this condition.

Clinical Features in Patients With PANDAS/PANS and Therapeutic Approaches: A Retrospective Study.

Objective: The clinical characteristics of patients with PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) and PANS (pediatric acute-onset neuropsychiatric syndrome) and the efficacy of antibiotic therapy with psychotherapy and antipsychotics were investigated to improve neurological symptoms as well as obsessive compulsive disorder (OCD). Methods: We retrospectively analyzed 62 patients with a clinical diagnosis of PANDAS/PANS enrolled from May 14, 2013 to September 15, 2020 in the Neurology Childhood Division, Department of Pediatrics at Sapienza, Rome. Clinical manifestations, neurological and psychiatric, laboratory investigations, and familiar history were collected to evaluate the differences between the two groups. The effects of various therapeutic approaches were examined. Descriptive and comparative statistical analyses were performed. Results: The mean age at onset of PANDAS/PANS symptoms was 6.2 ± 1.2 years. The most common diagnosis was PANDAS, followed by PANS. Neurological and psychiatric symptoms were mostly evident in both groups (>70% of the population), with no significant difference between them (P = 0.52 and P = 0.15, respectively). Irritability, aggressivity, and food restriction were more prevalent in children with PANS than in those with PANDAS (P = 0.024 and P = 0.0023, respectively). The levels of anti-streptolysin O and anti-DNAse B 10-fold higher in PANDAS than those in PANS (P < 0.0001). Antibiotics or psychotherapy were administered in most cases (90.3 and 53.2%, respectively), followed by antipsychotic treatments (24.2%). In the multivariate analysis, among the therapies used, psychotherapy significantly resulted in the most efficacious relief of OCD, reducing stress in patients and their parents (P = 0.042). Conclusion: Our findings confirm a clear clinical difference between the two groups, PANDAS and PANS, using different approaches. In fact, irritability, aggressivity, and food restriction were significantly more frequent in children with PANS and the levels of anti-streptolysin O and anti-DNAse B were higher in PANDAS. Another relevant finding is the efficacy of psychotherapy, especially for obsessive-compulsive disorder, and of antibiotic prophylaxis in managing acute neurological symptoms.

The Impact of the COVID-19 Epidemic During the Lockdown on Children With the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANDAS/PANS): The Importance of Environmental Factors on Clinical Conditions.

Introduction: In March 2020, SARS-CoV-2 declared a pandemic by the World Health Organization. Restrictive isolation measures have also brought psychological distress to the pediatric population. Building on the syndrome's characteristics, the present study explored the impact of lockdown on the clinical course of young people with PANDAS/PANS. The initial hypothesis considered both the reduced exposure to viral agents and the strategies of the parents and other containment actions as protective factors against the worsening of symptoms. Methods: One hundred and eight children, adolescents, and young adults were recruited according to the multicenter PANDAS/PANS research program. Parents participated in a web-based survey. Results: contrary to our hypothesis, the study results show an increase in symptoms during the block in 71% of the sample. Psychometric analyzes allowed us to exclude a relationship between the main symptoms of PANDAS and the increase in symptoms or the presence of symptoms before the block and their increase over time. The increase in symptoms is best explained by the presence of sleep disturbances and emotional lability. The exacerbation also appears to be linked to the onset of new symptoms in children and adolescents with depressed moods and eating problems. Furthermore, irritability and oppositionality are significant predictors of acute exacerbation. Equally statistically significant is the factor linked to the effects of pandemic stress, such as the fear of contracting the virus. No significant associations for symptom reduction have been identified between parental strategies or other parent-initiated actions, but the study demonstrates that caregiver perceived efficacy on the strategies used can reduce the risk of exacerbation. Conclusion: This preliminary study highlights the importance of studying the causes of increased symptoms in children with PANDAS/PANS. Life events can exacerbate the clinical condition or generate new symptoms in young patients. In particular, environmental, family, and social changes in the course of clinical symptoms in PANDAS/PANS patients should be investigated. It highlights the importance of emotional and behavioral management, which can be improved by enhancing coping strategies in young people with PANDAS/PANS and their caregivers through a combination treatment in which CBT and PMT are included, in line with guidelines. Limits: An experimental proxy-report questionnaire not yet standardized and validated on the PANS/PANDAS pediatric clinical sample was used for the exploratory study. There is also a small sample size (N = 108) and the absence of a control group (pre-lockdown or children without PANDAS/PANS). It would be interesting to evaluate the exact long-term dimensions to see the course of symptoms after covid and conduct a new study focusing on the impact of stressful events on the clinical course of the syndrome.

Breastfeeding in Pediatric Acute-Onset Neuropsychiatric Syndrome: An Italian Observational Study.

Objective: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a condition defined by sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms. Its pathogenesis is unknown but it seems triggered by infections, metabolic disturbances, and other inflammatory reactions. PANS represents a neurodevelopmental problem and infant feeding can play a role. Breast milk is the ideal food for infants and influences children's brain, cognitive, and socio-emotional development. Methods: We enrolled 52 children diagnosed with PANS. We interviewed their parents in order to investigate perinatal history, infant feeding, neurologic development, and confounding factors like socio-economic status and region of origin. We subgrouped PANS patients into three subsets: those who only received human milk (HMO), those who only received infant formula, and those who received mixed feeding. Results: The cohort is composed of 78.9% males, with a median age of 11 years (range 7-17). We found some neurodevelopmental problems (13.5%): walking disorders, ASD, ADHD, oppositional attitude, and delayed psychomotor development. We found scholar performance deficits (25%), including language problems like dysgraphia, dyslexia, and dyscalculia. The achievement of some milestones in the development of the infant is affected in 73.1% of cases. Breastfeeding is not homogeneously practiced in Italy because of social, economic, and cultural phenomena. The richest and the poorest families (100%) in the sample choose breastfeeding, probably with a different approach and for different reasons (awareness or need). In the group of PANS patients fed with HMO, compared to the rest of the patients, we registered fewer cases of growth problems (0 vs. 12.9%; p = 0.14), school performance problems or the need for school support (19.1% vs. 29%; p = 0.42), and a delay in the age of babbling/speaking (range 4-20 vs. 7-36 months; p = 0.066). Conclusion: This is the first study that investigates the role of breastfeeding in the development of PANS. Promoting breastfeeding is important in the general population and also in PANS patients because it has an important social and global health impact, also during adult life. Further studies with a bigger population are needed to investigate the mechanisms underlying PANS and the role that breastfeeding may play in their short- and long-term neurodevelopment.

Gaming among Children and Adolescents during the COVID-19 Lockdown: The Role of Parents in Time Spent on Video Games and Gaming Disorder Symptoms.

It is mainly children and adolescents who are involved in video gaming. The lockdown caused by the COVID-19 pandemic may have further increased their use of video games and, consequently, the risk of gaming disorder (GD) symptoms. However, currently, we do not have exhaustive knowledge of this issue. To fill this gap, the current study aims to analyze video gaming habits in children and adolescents during the lockdown, starting in March 2020 in Italy, the first European country affected by the pandemic. Specifically, we aim to understand how variables related to parents-for instance, knowledge of their offspring's life, the monitoring of their video gaming habits, and parental use of video games-are related to their offspring's time spent on video games and GD symptoms. A web-based survey involving parents (n = 554, 79% mothers, mean age = 45.39) of 554 children and adolescents (73% males, mean age = 11.11) was utilized. The results showed that they were involved in video games, particularly boys and adolescents, with high rates of GD symptoms. The parents also spent a considerable amount of time playing video games. A path model that explained the mechanisms through which parental variables were related to their offspring's time spent on video games and GD symptoms, controlling for gender and age, was verified. Overall, the findings indicate the importance of educating parents to behave effectively with respect to video games and monitor their offspring's video gaming habits.

Myoclonic Epilepsy: Case Report of a Mild Phenotype in a Pediatric Patient Expanding Clinical Spectrum of KCNA2 Pathogenic Variants.

We report on the rare case of a male toddler presenting with myoclonic epilepsy characterized by daily episodes of upward movements of the eyebrows, and myoclonic jerks of both head and upper limbs. In addition, the child showed speech delay, tremors, and lack of motor coordination. Next Generation Sequencing analysis (NGS) performed in trio revealed in the proband the c.889C>T de novo missense variant in the KCNA2 gene in heterozygous state. This is the first case of myoclonic epilepsy in a toddler due to a c.889C>T KCNA2 missense variant. The patient was treated with valproic acid and ethosuximide with a good clinical response. At 6 years old, follow-up revealed that the proband was seizure-free with tremors and clumsiness in movements. According to the literature, this case supports the correlation between myoclonic epilepsy and KCNA2 alterations. This evidence suggests that performing genomic testing including the KCNA2 gene in preschool patients affected by myoclonic epilepsy, especially when associated with delayed neurodevelopment. Our goal is to expand the phenotypical spectrum of this rare condition and adding clinical features following a genotype-first approach.

Oxidative stress and gut-derived lipopolysaccharides in children affected by paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.

BACKGROUND: Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to evaluate serum NOX2 levels, as well as 8-iso-prostaglandin F2α (8-iso-PGF2α) and lipopolysaccharide (LPS) of PANDAS patients. METHODS: In this study we wanted to compare serum levels of soluble NOX2-dp (sNOX-2-dp), iso-PGF2α and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used as intestinal permeability assay. RESULTS: Compared with CT, PANDAS children had increased serum levels of sNOX-2-dp, 8-iso-PGF2α and LPS. Bivariate analysis showed that serum sNOX2-dp was significantly correlated with LPS (Rs = 0.359; p = 0.005), zonulin (Rs = 0.444; p < 0.001) and 8-iso-PGF2α (Rs = 0.704; p < 0.001). Serum LPS significantly correlated with zonulin (Rs = 0.610; p < 0.001), and 8-iso-PGF2α (Rs = 0.591; p = 0.001). Finally, a multiple linear regression analysis showed that serum 8-iso-PGF2α and zonulin were the only independent variables associated with sNOX2-dp (R2 = 68%). CONCLUSION: This study shows that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be involved in the process of neuroinflammation.

Small 7p22.3 microdeletion: Case report of Snx8 haploinsufficiency and neurological findings.

Some cases of chromosome 7p22.3 deletions have been reported, but the genotype-phenotype correlation is still uncertain. Neurodevelopmental delay and heart anomalies have been recorded as the most recurrent defects. We describe the clinical features of a four-year-old male child with a 139 kb deletion at 7p22.3 involving SNX8 gene, inherited from a mosaic mother. The same deletion is also present in the fetus on the ongoing third pregnancy of the couple with normal fetal ultrasound assessment. The proband was prenatally diagnosed with left kidney agenesis. He does not show any congenital heart disease, but mild intellectual disability, learning and language delay, and severe behavioral problems related to the hyperactive-impulsive and inattentive area. These clinical features are also evident in other 7p22 deletions cases involving the SNX8 gene, supporting the role of this gene in neurodevelopment. Conversely, the revision of all published cases with small 7p22 deletions and the absence of heart malformations in the present family confirm that this region is involved in heart development, anyway did not confirm the role of SNX8 in cardiac phenotypes, either due to the reduced penetrance or the involvement of other candidate genes.

Dilated Virchow-Robin spaces in children with seizures. A possible correlation?

HYPOTHESIS: Virchow-Robin spaces (VRS) are perivascular spaces in the brain and can normally be visualized in Magnetic Resonance Imaging (MRI). Dilated VRS (dVRS) are defined on the basis of their shape, and can rarely be observed in healthy subjects, or found in various diseases. A judgement of their role may derive from the appearance of the adjacent cerebral tissue and from the clinical context. OBJECTIVE: To define a correlation between the presence of dVRS and the clinical, EEG and MRI features in children with seizures. MATERIALS AND METHODS: We retrospectively analyzed the clinical, electroencephalographic and additional neuroradiological features of a group of 30 children with seizures and dVRS. Six patients repeated the MRI because of persistent drug-refractory seizures. RESULTS: 26/30 patients had epilepsy, 4/30 patients had febrile seizures. dVRS were localized in basal ganglia in 10/30 cases and in supratentorial white matter in 16/30 cases. In 4/30 cases dilated VRS were present in both the zones. Associated MRI anomalies were reported in 11/30 patients, not necessary involving the adjacent tissue. A correlation between epileptic focus and side of VRS was present in 5/30 patients only. Unmodified VRS were observed in the 6 patients who underwent a second MRI. CONCLUSION: In children with seizures, dVRS may be observed in basal ganglia or, mainly, in supratentorial white matter. However, also in this class of patients dVRS appear to be a non-progressive findings and not connected with the main seizures-related features of the patients.

Focus on Cardiologic Findings in 30 Children With PANS/PANDAS: An Italian Single-Center Observational Study.

Objective: Cardiac involvement in PANS has not been clarified relying on the scientific literature available until today. It is known that streptococcal infections play a role in the etiology of a great number of diseases including Sydenham chorea and rheumatic fever, among others. Based on the suspected pathogenesis of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) reported in the medical literature, we decided to investigate the cardiologic involvement in children with a recent PANS/PANDAS diagnosis. Methods: The study population satisfies PANS (1) and PANDAS (2) criteria of diagnoses. Cardiologic assessment was performed through clinical examination, electrocardiography, and echocardiography. Results: In the selected pediatric population, a significant number of children presented mitral valve involvement, systolic murmurs and electrocardiographic abnormalities. High ASLOT levels did not seem to be associated to a cardiac involvement. Conclusions: Often PANS is difficult to diagnose because it is little known by physicians and most of the cardiologic findings described in this study are common among the healthy pediatric population. Also, ASLOT levels seems not to be predictive of cardiac involvement. Furthermore, the existence of PANDAS as a clinical entity is associated with a group of anti-neuronal autoantibodies found in Sydenham chorea is still controversial. We recommend a complete cardiologic evaluation in those children who meet the PANS/PANDAS diagnostic criteria.

Could Rolandic spikes be a prognostic factor of the neurocognitive outcome of children with BECTS?

INTRODUCTION: Rolandic epilepsy, also known as benign childhood epilepsy with centrotemporal spikes (BECTS), is one of the most common epileptic syndromes in previously healthy children. Despite what was known about the benignity of this syndrome, there is always more evidence about the involvement of the cognitive functions with different deficits in several domains to be investigated. AIM OF THE STUDY: The aim of our study was to describe prognostic electroencephalogram (EEG) pattern of an adverse cognitive development to recognize patients at higher risk of lasting cognitive deficits that could need antiepileptic drugs (AEDs) or an improved neurocognitive therapy. In addition, we wanted to investigate the existence of a possible linkage between the number of interictal epileptiform discharges (IEDs) in the EEG and the more pronounced cognitive deficits. MATERIAL AND METHODS: We performed a case-control study on a cohort of 16 patients (10 male and 6 female) aged 4-14, diagnosed with BECTS who underwent EEG, magnetic resonance imaging (MRI), and neurocognitive assessment at the Pediatric Neurology Unit at the Umberto I Hospital, Sapienza University of Rome. Patients were divided into two groups according to the percentage of IEDs evaluated based on their sleep EEG: group A with less than 50% of the entire EEG invaded by discharges in more than 70% of the total number of EEG performed, so-called with low or intermediate activation. On the contrary, group B had a high activation, with more than 50% of the entire EEG invaded by discharges in the same percentage of the EEG performed. All children were assessed based on a protocol designed to study neuropsychological functions with specific tests chosen depending on age (Wechsler Intelligence Scale for Children IV: WISC IV; Wechsler Preschool and Primary Scale of Intelligence III: WPPSI III). Groups were compared for cognitive outcomes achieved by each patient through Student's t-test with a significance level of p<0.05 (two-tailed). RESULTS: There is no statistically significant difference in the cognitive outcomes of these patients: Student's t-test showed a statistical significance (p) for each cognitive index always higher than 0.05, demonstrating that the intellectual quotient (IQ) and all other indexes analyzed (verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI)) are not affected by the difference in EEG anomalies presented by our patients. Interestingly, all patients had an IQ equal to or greater than the Italian average (12 out of 16 patients showed an IQ>100), with selective drops, particularly significant in the WMI and also in the PSI. CONCLUSIONS: Our results clearly demonstrate the importance of a proper evaluation of patients with this kind of epilepsy, without paying attention only to those with the greatest number of IEDs or seizures because all of them had a neurocognitive impairment, especially in memory. These data may be reinforced by a larger sample for an even more significant statistical value. These results also highlight the importance of a neurocognitive therapy for these children to treat for their specific needs.