Ataxia Telangiectasia Arising as Immunodeficiency: The Intriguing Differential Diagnosis.

Ataxia telangiectasia (AT) is a rare disease characterized by the early onset and slow progression of neurodegenerative defects, mainly affecting the cerebellum, associated with immunodeficiency and teleangiectasias. Ataxia is the hallmark of the disease and usually its first manifestation. Overt cerebellar ataxia usually becomes evident between 16 and 18 months of age, after the onset of walking, and is characterized by frequent falls and an ataxic gait with an enlarged base. We report the case of a child who first presented with serious recurrent infectious, without exhibiting neurological symptoms. The patient was initially diagnosed with combined immunodeficiency (CID) of unknown etiology for nearly 3 years, before he was definitively diagnosed with ataxia telangiectasia.

Congenital Myopathy as a Phenotypic Expression of CACNA1S Gene Mutation: Case Report and Systematic Review of the Literature.

BACKGROUND: Congenital myopathies are a group of clinically, genetically, and histologically heterogeneous diseases caused by mutations in a large group of genes. One of these is CACNA1S, which is recognized as the cause of Dihydropyridine Receptor Congenital Myopathy. METHODS: To better characterize the phenotypic spectrum of CACNA1S myopathy, we conducted a systematic review of cases in the literature through three electronic databases following the PRISMA guidelines. We selected nine articles describing 23 patients with heterozygous, homozygous, or compound heterozygous mutations in CACNA1S and we added one patient with a compound heterozygous mutation in CACNA1S (c.1394-2A>G; c.1724T>C, p.L575P) followed at our Institute. We collected clinical and genetic data, muscle biopsies, and muscle MRIs when available. RESULTS: The phenotype of this myopathy is heterogeneous, ranging from more severe forms with a lethal early onset and mild-moderate forms with a better clinical course. CONCLUSIONS: Our patient presented a phenotype compatible with the mild-moderate form, although she presented peculiar features such as a short stature, myopia, mild sensorineural hearing loss, psychiatric symptoms, and posterior-anterior impairment gradient on thigh muscle MRI.

Children under 6 years with acute headache in Pediatric Emergency Departments. A 2-year retrospective exploratory multicenter Italian study.

BACKGROUND: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. METHODS: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. RESULTS: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. CONCLUSION: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought.

Digital Devices Use and Fine Motor Skills in Children between 3-6 Years.

(1) Background: The principal aim of our research was to explore the relationship between digital devices use and fine motor skills in children aged three to six years and to explore the effect of some socio-demographic factors. (2) Methods: we enrolled 185 children aged between three to six years. The parents of all the participants fulfilled a questionnaire to explore the digital device use, and their children performed a standardized test to assess fine motor skills (APCM-2). We performed the Spearman correlation test to explore the relationship between different variables. (3) Results: the children spent an average of 3.08 ± 2.30 h/day on digital devices. We did not find a significant association between the time of use of digital devices and fine motor skills (p = 0.640; r = -0.036). The youngest children experienced digital tools earlier than older ones (p < 0.001; r = 0.424) and they were also the ones who used digital tools more time afterwards (p = 0.012; -0.202). The children who had working parents spent more time on digital devices (p = 0.028; r = 0.164/p = 0.037; r = 0.154) and used digital devices earlier (p = 0.023; r = 0.171). (4) Conclusions: This data suggest that it would be useful to monitor the use of digital tools, especially in the very first years of life. Future studies are needed to further explore this topic.

Essential headaches in developmental age: What is changed before, during and after the lockdown for COVID-19 pandemic. Clinical study.

Introduction: Essential headache is one of the main causes of pain in children, and has an important impact on their quality of life. In children with essential headaches play an important role in both triggers like stress, excessive use of video terminals, or physical fatigue but also comorbidities like anxiety, depression, and sleep disturbances. CoViD-19 Pandemic was very stressful, especially for children, and amplified all headache triggers and comorbidities. Study objective: In this work, we studied the aspects concerning the headache,lifestyle, habits, and mental health of children before, during, and after the lockdown and the differences between some categories (selected by age, gender, and headache status before the lockdown). Methods: This study was conducted on 90 patients with primary headaches followed at the AOUP Neuropediatrics Clinic from January 2018 to March 2022. Participants answered a questionnaire of 21 questions. For every question, the answer was divided into three periods: before, during, or after the lockdown. All dates have been converted and inserted into a database and we used SPSS technology for statistical analysis. Results: In our study, 51,1% were females and 48,9% were males and there was a prevalence of adolescents (56,7%) compared to children from 5 to 11 years (43,3%). Regarding the headache onset, 77,7% of patients started to suffer from headaches before 10 years, moreover, 68,9% had familiarity with the headache. Using Cohen's K- Concordance Test, we performed a Concordance Analysis, studying the questions in the three periods above mentioned: considering headache characteristics there is poor concordance about the trend of headache; modest concordance (K: 0,2-0,4) about the frequency and the type (migraine or tension headache); moderate concordance (K: 0,41-0,61) about the acute use of analgesic. Analyzing lifestyle the lockdown had a significant impact on sports (practiced much less) and on the use of video terminals (used much more). Conclusion: The pandemic and lockdown aren't events that led to strong and unidirectional responses in patients, there is great variability in the answers about headache, lifestyle, and psychology, and each patient had individualized reactions. However, these considerations are not applied to physical activity and the use of video terminals, because both have been inevitably modified by the pandemic situations and so were not affected by subjective influence.

Long-term effectiveness of add-on perampanel in patients with Lennox-Gastaut syndrome: A multicenter retrospective study.

This retrospective study assessed long-term effectiveness of add-on perampanel (PER) in patients with Lennox-Gastaut syndrome (LGS). Outcomes included time to PER failure and time to seizure relapse in responders. PER failure was defined as either discontinuation of PER or initiation of another treatment. Seizure relapse in responders was defined as occurrence of a seizure in seizure-free patients and increase of at least 50% in average monthly seizure frequency for those who were responders. Eighty-seven patients were included. Treatment failure occurred in 52 (59.8%) subjects at a median time of 12 months. Treatment failure was due to lack of efficacy in 27 (52.0%) patients, lack of tolerability in 14 (27.0%), and both reasons in 11 (21.0%). A slower titration was associated with a lower risk of PER failure compared to faster titration schedules, and the occurrence of adverse events increased the risk of treatment failure. Thirty-six patients (41.4%) were responders during a median follow-up of 11 months. Seizure relapse occurred in 13 of 36 (36.1%) patients after a median time of 21 months. The overall rate of seizure responders was 23 of 87 (26.4%) at the end of follow-up. This study provides real-world evidence on the effectiveness of PER as adjunctive treatment in LGS patients.

Neurovisual Manifestations in Children with Mild COVID-19: An Association to Remember.

Neurovisual involvement has been reported in a number of patients with severe SARS-CoV-2 disease (COVID-19), mainly among adult patients. In children, such involvement has been reported in rare cases, often in those presenting with severe forms of COVID-19. The aim of this work is to explore the association between mild COVID-19 and neurovisual manifestations. We report the cases of three previously healthy children who developed neurovisual manifestations following mild acute COVID-19, analysing the clinical phenotype, the latency between the onset of acute COVID-19 and neurovisual involvement, and the kinetic of resolution. Our patients developed different clinical patterns, including visual impairment and ophthalmoplegia. In two cases, these clinical features occurred during acute COVID-19, while in the third patient their development was delayed after 10 days from disease onset. Furthermore, the dynamics of resolution were different, with one patient showing remission after 24 hours, the second after 30 days, and the third showing persistence of the strabismus after 2 months of follow-up. The spreading of COVID-19 among the paediatric population will probably lead to an increase of atypical disease forms, including those presenting with neurovisual involvement. Therefore, a better knowledge of the pathogenic and clinical features of these manifestations is warranted.

Phenotypic Spectrum of NFIA Haploinsufficiency: Two Additional Cases and Review of the Literature.

The NFIA (nuclear factor I/A) gene encodes for a transcription factor belonging to the nuclear factor I family and has key roles in various embryonic differentiation pathways. In humans, NFIA is the major contributor to the phenotypic traits of "Chromosome 1p32p31 deletion syndrome". We report on two new cases with deletions involving NFIA without any other pathogenic protein-coding gene alterations. A cohort of 24 patients with NFIA haploinsufficiency as the sole anomaly was selected by reviewing the literature and public databases in order to analyze all clinical features reported and their relative frequencies. This process was useful because it provided an overall picture of the phenotypic outcome of NFIA haploinsufficiency and helped to define a cluster of phenotypic traits that can facilitate clinicians in identifying affected patients. NFIA haploinsufficiency can be suspected by a careful observation of the dysmorphisms (macrocephaly, craniofacial, and first-finger anomalies), and this potential diagnosis is strengthened by the presence of intellectual and developmental disabilities or other neurodevelopmental disorders. Further clues of NFIA haploinsufficiency can be provided by instrumental tests such as MRI and kidney urinary tract ultrasound and confirmed by genetic testing.

Psychopathological Impact in Patients with History of Rheumatic Fever with or without Sydenham's Chorea: A Multicenter Prospective Study.

Sydenham's chorea (SC) is a post-streptococcal autoimmune disorder of the central nervous system, and it is a major criterium for the diagnosis of acute rheumatic fever (ARF). SC typically improves in 12-15 weeks, but patients can be affected for years by persistence and recurrencies of both neurological and neuropsychiatric symptoms. We enrolled 48 patients with a previous diagnosis of ARF, with or without SC, in a national multicenter prospective study, to evaluate the presence of neuropsychiatric symptoms several years after SC's onset. Our population was divided in a SC group (n = 21), consisting of patients who had SC, and a nSC group (n = 27), consisting of patients who had ARF without SC. Both groups were evaluated by the administration of 8 different neuropsychiatric tests. The Work and Social Adjustment Scale (WSAS) showed significantly (p = 0.021) higher alterations in the SC group than in the nSC group. Furthermore, 60.4% (n = 29) of the overall population experienced neuropsychiatric symptoms other than choreic movements at diagnosis and this finding was significantly more common (p = 0.00) in SC patients (95.2%) than in nSC patients (33.3%). The other neuropsychiatric tests also produced significant results, indicating that SC can exert a strong psychopathological impact on patients even years after its onset.

The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series.

Introduction: Stroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (≥500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and Methods: We retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. Results: The underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4-34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (± 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (± 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. Conclusions: SLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management.

Case Report: MIS-C With Prominent Hepatic and Pancreatic Involvement in a Vaccinated Adolescent - A Critical Reasoning.

Multisystem inflammatory syndrome in children (MIS-C) is a pathologic condition that has emerged during the coronavirus disease 2019 (COVID-19) pandemic. Although the epidemiological evidence of association between MIS-C and SARS-CoV-2 infection has been demonstrated, its pathogenic mechanism is still undefined. We describe the case of a 17-year old female, previously vaccinated against SARS-CoV-2, presenting with a history of asthenia, fever, cough, anorexia, abdominal pain, and vomiting. During the hospitalization, the patient developed bilateral conjunctivitis, hand vasculitis, cutaneous rash, and multiple pulmonary nodules, following by hepatitis and pancreatitis. As she reported a high-risk contact with a SARS-CoV-2 positive patient 10 days before admission, the epidemiological link and the clinical picture characterized by multi-system organ disfunction and inflammatory biomarkers increase led us to the diagnosis of MIS-C. Therefore, the patient was treated with intravenous immunoglobulin and corticosteroids, resulting in a rapid resolution of fever, cutaneous, and pulmonary involvement, while the recovery of hepatitis and pancreatitis was observed in the following weeks. This case leads to the discussion on whether SARS-CoV-2 immunized children and adolescents should be considered at risk of developing MIS-C and on their possible presentation with non-classic clinical features. Additionally, due to the increasing number of vaccinated children and adolescents, the issues resulting either from the diagnostic suspect of MIS-C or from the consequent need of an early therapeutic approach are discussed.

Targeting Inflammatory Mediators in Epilepsy: A Systematic Review of Its Molecular Basis and Clinical Applications.

Introduction: Recent studies prompted the identification of neuroinflammation as a potential target for the treatment of epilepsy, particularly drug-resistant epilepsy, and refractory status epilepticus. This work provides a systematic review of the clinical experience with anti-cytokine agents and agents targeting lymphocytes and aims to evaluate their efficacy and safety for the treatment of refractory epilepsy. Moreover, the review analyzes the main therapeutic perspectives in this field. Methods: A systematic review of the literature was conducted on MEDLINE database. Search terminology was constructed using the name of the specific drug (anakinra, canakinumab, tocilizumab, adalimumab, rituximab, and natalizumab) and the terms "status epilepticus," "epilepsy," and "seizure." The review included clinical trials, prospective studies, case series, and reports published in English between January 2016 and August 2021. The number of patients and their age, study design, specific drugs used, dosage, route, and timing of administration, and patients outcomes were extracted. The data were synthesized through quantitative and qualitative analysis. Results: Our search identified 12 articles on anakinra and canakinumab, for a total of 37 patients with epilepsy (86% febrile infection-related epilepsy syndrome), with reduced seizure frequency or seizure arrest in more than 50% of the patients. The search identified nine articles on the use of tocilizumab (16 patients, 75% refractory status epilepticus), with a high response rate. Only one reference on the use of adalimumab in 11 patients with Rasmussen encephalitis showed complete response in 45% of the cases. Eight articles on rituximab employment sowed a reduced seizure burden in 16/26 patients. Finally, one trial concerning natalizumab evidenced a response in 10/32 participants. Conclusion: The experience with anti-cytokine agents and drugs targeting lymphocytes in epilepsy derives mostly from case reports or series. The use of anti-IL-1, anti-IL-6, and anti-CD20 agents in patients with drug-resistant epilepsy and refractory status epilepticus has shown promising results and a good safety profile. The experience with TNF inhibitors is limited to Rasmussen encephalitis. The use of anti-α4-integrin agents did not show significant effects in refractory focal seizures. Concerning research perspectives, there is increasing interest in the potential use of anti-chemokine and anti-HMGB-1 agents.

Peripheral Arterial Tonometry (EndoPAT)-measured Endothelial Dysfunction in Migraine with Aura children.

BACKGROUND: The association between Migraine with Aura (MA) and vascular disease has been previously reported. We investigated whether pre-clinical vascular alterations, such as Endothelial Dysfunction, are already present in children and adolescents with Migraine with Aura. METHODS: We retrospectively enrolled 27 patients having Migraine with Aura, aged9 -18 years, and 31 age matched healthy control subjects to evaluateEndothelial Function by Peripheral Arterial Tonometry. This technique measures finger pulse wave amplitude, before and during reactive hyperaemia, and calculates the Augmentation Index (AI) and the Reactive Hyperaemia Index (RHI). We also set-up an Aura Severity Scale to assess disease severity and its relationship with AI and RHI alterations. RESULTS: Also if the case-control study resulted only partially as significant, we found there is an inversely proportional relationship between the severity of the migraine measured with Aura Severity Scale and the values of the endoscore (a significantly reduced levels of AI (p-value <0,03) and a marginal reduction of RHI levels (p-value <0,07). CONCLUSION: Further studies should explore the impact of pre-clinical vascular alterations in children and adolescents with Migraine with Aura.

Pediatric traumatic brain injury: a new relation between outcome and neutrophil-to-lymphocite ratio.

Leading causes of death in industrialized countries are traumatic injuries and acquired disability, and entry to the emergency department in childhood. TBI (traumatic brain injury) may involve the onset of both primary lesions and a complex immune response (sterile immune reaction to brain injury), which, in addition to neuro-protective effects, can mediate secondary neurological injury. The neutrophil-to-lymphocyte ratio (NLR), as a circulating inflammatory marker, has been related to outcomes in adult patients with non-neurologic diseases (such as gut tumours) or neurologic diseases (such as stroke or brain tumours), and to the prognosis of traumatic brain injury in adolescents and adults. However, the potential role of NLR in predicting outcomes in paediatric head trauma is not clearly defined. The aim of this retrospective observational study is to evaluate the association between clinical features predictive of intracranial and extracranial lesions in TBI and NLR and to establish whether an elevation of NLR is indirectly associated with adverse outcomes in pediatric patients with TBI. We analysed a sample of 219 pediatric patients, between 2-18 years old, after a TBI, and evaluated if differences in NLR were associated with neurological signs or positive CT in pediatric patients. We then compared the NLR values ​​between healthy subjects and patients with TBI.

PRES-like leukoencephalopathy presenting with status epilepticus associated with Brentuximab Vedotin treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) is characterized by acute neurological symptoms with typical imaging features, primarily in the territories of the brain supplied by the posterior circulation, probably due to vasogenic edema. Both clinical and imaging features are generally reversible. We report a 13-year-old girl affected by Nodular Sclerosis Classical Hodgkin Lymphoma stage IIIB into complete remission, with a recurrence and autologous bone-marrow transplantation, who has been treated with an anti-CD30 monoclonal antibody, brentuximab-vedotin. The girl has suddenly presented a convulsive status epilepticus, that needed intubation and sedation. Therefore, an IV therapy with levetiracetam was started. Furthermore, the girl has presented high blood pressure and reduced kidney function. Brain MRI demonstrated a diffuse PRES-like disease, that went into regression after the first week. After another week, the girl presented a new prolonged generalized tonic clonic convulsive episode, that needed intubation and sedation and an association of clobazam and levetiracetam: a new brain MRI showed a recurrence of PRES-like lesions in addition to some signs of leukoencephalopathy with brain lactate accumulation on 1H-MRS, due to cerebral energetic failure. The girl also presented a refractory arterial hypertension. After 45 days of ICU hospitalization the patient has been discharged and followed up with neurological examinations. Brain MRI and brain 1H-MRS, 5 months after patient's discharge, showed incomplete regression of cerebral white matter signal abnormalities with MRS normalization.

Therapeutic aspects of Sydenham's Chorea: an update.

Sydenham's Chorea (SC) is a hyperkinetic movement disorder associated with neuropsychiatric manifestations. It is believed to be caused by the autoimmune response following a group A beta-hemolytic streptococcal (GABHS) pharyngitis, and it is one of the major diagnostic criteria for Acute Rheumatic Fever (ARF) diagnosis. Despite having been known and studied for centuries, there are still no standardized therapies or official guidelines for SC treatment, so that it is necessarily left to physicians' clinical experience. Antibiotic treatment, symptomatic therapies, and immunomodulatory treatment are the three pillars upon which SC patients' management is currently based, but they still lack a solid scientific basis. The aim of this writing is precisely to review the state of the art of SC's treatment, with an overview of the advances made in the last 5 years. However, since the therapeutic uncertainties are a mere reflection of the severe gap of knowledge that concerns SC's pathogenesis and manifestations, the importance of high-quality research studies based on homogenized methodologies, instruments, and measured outcomes will also be stressed.

Expanding Phenotype of Poirier-Bienvenu Syndrome: New Evidence from an Italian Multicentrical Cohort of Patients.

BACKGROUND: Poirier-Bienvenu Neurodevelopmental Syndrome (POBINDS) is a rare disease linked to mutations of the CSNK2B gene, which encodes for a subunit of caseinkinase CK2 involved in neuronal growth and synaptic transmission. Its main features include early-onset epilepsy and intellectual disability. Despite the lack of cases described, it appears that POBINDS could manifest with a wide range of phenotypes, possibly related to the different mutations of CSNK2B. METHODS: Our multicentric, retrospective study recruited nine patients with POBINDS, detected using next-generation sequencing panels and whole-exome sequencing. Clinical, laboratory, and neuroimaging data were reported for each patient in order to assess the severity of phenotype, and eventually, a correlation with the type of CSNK2B mutation. RESULTS: We reported nine unrelated patients with heterozygous de novo mutations of the CSNK2B gene. All cases presented epilepsy, and eight patients were associated with a different degree of intellectual disability. Other features detected included endocrinological and vascular abnormalities and dysmorphisms. Genetic analysis revealed six new variants of CSNK2B that have not been reported previously. CONCLUSION: Although it was not possible to assess a genotype-phenotype correlation in our patients, our research further expands the phenotype spectrum of POBINDS patients, identifying new mutations occurring in the CSNK2B gene.

Efficacy of Liposomal Melatonin in sleep EEG in Childhood: A Double Blind Case Control Study.

Electroencephalography (EEG) is pivotal in the clinical assessment of epilepsy, and sleep is known to improve the diagnostic yield of its recording. Sleep-EEG recording is generally reached by either partial deprivation or by administration of sleep-inducing agents, although it is still not achieved in a considerable percentage of patients. We conducted a double-blind placebo-controlled study, involving a hundred patients between 1 and 6 years old, randomized into two groups: Group 1 received liposomal melatonin (melatosome) whereas Group 2 received a placebo. Sleep latency (SL), defined as the time span between the onset of a well-established posterior dominant rhythm, considered as a frequency of 3 to 4 Hz, increasing to 4-5 Hz by the age of 6 months, to 5-7 Hz by 12 months, and finally to 8 Hz by 3 years, and the first EEG sleep figures detected, were measured for each patient. A significant difference in SL was observed (10.8 ± 5 vs. 18.1 ± 13.4 min, p-value = 0.002). Within each group, no differences in sleep latency were detected between genders. Furthermore, no difference in EEG abnormality detection was observed between the two groups. Our study confirmed the efficacy and safety of melatonin administration in sleep induction. Nonetheless, liposomal melatonin presents a greater bioavailability, ensuring a faster effect and allowing lower dosages. Such results, never before reported in the literature, suggest that the routine employment of melatonin might improve clinical practice in neurophysiology, reducing unsuccessful recordings.

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

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.