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Background: CACNA1A-related disorders present with persistent progressive and non-progressive cerebellar ataxia and paroxysmal events: epileptic seizures and non-epileptic attacks. These phenotypes overlap and co-exist in the majority of patients., Objective: To describe phenotypes in infantile onset CACNA1A-related disorder and to explore intra-familial variations and genotype-phenotype correlations., Material and Methods: This study was a multicenter international collaboration. A retrospective chart review of CACNA1A patients was performed. Clinical, radiological, and genetic data were collected and analyzed in 47 patients with infantile-onset disorder., Results: Paroxysmal non-epileptic events (PNEE) were observed in 68% of infants, with paroxysmal tonic upward gaze (PTU) noticed in 47% of infants. Congenital cerebellar ataxia (CCA) was diagnosed in 51% of patients including four patients with developmental delay and only one neurological sign. PNEEs were found in 63% of patients at follow-up, with episodic ataxia (EA) in 40% of the sample. Cerebellar ataxia was found in 58% of the patients at follow-up. Four patients had epilepsy in infancy and nine in childhood. Seven infants had febrile convulsions, three of which developed epilepsy later; all three patients had CCA. Cognitive difficulties were demonstrated in 70% of the children. Cerebellar atrophy was found in only one infant but was depicted in 64% of MRIs after age two., Conclusions: Nearly all of the infants had CCA, PNEE or both. Cognitive difficulties were frequent and appeared to be associated with CCA. Epilepsy was more frequent after age two. Febrile convulsions in association with CCA may indicate risk of epilepsy in later childhood. Brain MRI was normal in infancy. There were no genotype-phenotype correlations found., (Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

The temporomandibular joint (TMJ) is a bilateral synovial articulation stabilized by several anatomical structures such as ligaments. The existence of articular capsule reinforcement structures have been described in the lateral and medial sides of disc which have been defined as collateral ligaments, lateral and medial. Despite that, some macroscopic observations support that these collateral ligaments do not belong to the articular capsule but they belong to the disc. By that, the aim of the present work was to evaluate morphological aspects of TMJ from cadaveric frozen heads by histological and immunofluorescence techniques in order to verify the origin and insertion of lateral and medial collateral ligaments. Results show that both lateral and medial ligaments origin from the disc and insert directly to the articular cartilage of mandibula condyle. These data open a new approach in the study of human TMJ.

Neurons are particularly susceptible to microtubule (MT) defects and deregulation of the MT cytoskeleton is considered to be a common insult during the pathogenesis of neurodegenerative disorders. Evidence that dysfunctions in the MT system have a direct role in neurodegeneration comes from findings that several forms of neurodegenerative diseases are associated with changes in genes encoding tubulins, the structural units of MTs, MT-associated proteins (MAPs), or additional factors such as MT modifying enzymes which modulating tubulin post-translational modifications (PTMs) regulate MT functions and dynamics. Efforts to use MT-targeting therapeutic agents for the treatment of neurodegenerative diseases are underway. Many of these agents have provided several benefits when tested on both in vitro and in vivo neurodegenerative model systems. Currently, the most frequently addressed therapeutic interventions include drugs that modulate MT stability or that target tubulin PTMs, such as tubulin acetylation. The purpose of this review is to provide an update on the relevance of MT dysfunctions to the process of neurodegeneration and briefly discuss advances in the use of MT-targeting drugs for the treatment of neurodegenerative disorders.

Inositol polyphosphate-5-phosphatase K [ INPP5K (MIM: 607875)] acts as a PIP 3 5-phosphatase and regulates actin cytoskeleton, insulin, and cell migration. Biallelic pathogenic variants in INPP5K have recently been reported in patients affected by a form of muscular dystrophy with childhood onset. Affected patients have limb girdle muscle weakness, often associated with bilateral cataracts, short stature, and intellectual disability. Here we report four patients affected by INPP5K -related muscle dystrophy, who were apparently unrelated but originated from the same geographical area in South Italy. These patients manifest a recognizable phenotype characterized by early onset muscular dystrophy associated with short stature and intellectual disability. All affected subjects were homozygous or compound heterozygous for the c.67G > A (p.Val23Met) missense change and shared a common haplotype, indicating the occurrence of a founder effect., (Copyright © 2020 D’Amico, Fattori, Nicita, Barresi, Tasca, Verardo, Pizzi, Moroni, De Mitri, Frongia, Pane, Mercuri, Tartaglia and Bertini.)

The orthodontic tooth movement is the last step of several biological processes that take place after the application of external forces. During this process, dental pulp tissue is subjected to structural and protein expression modifications in order to maintain their integrity and functional morphology. The purpose of the present work was to perform an in vivo study, evaluating protein expression modifications in the human dental pulp of patients that have undergone orthodontic tooth movement due to pre-calibrated light force application for 30 days. Dental pulp samples were extracted from molars and premolars of the control group and after 7 and 30 days of treatment; the samples were then processed for immunofluorescence reactions using antibodies against fibronectin, collagen I and vascular endothelial growth factor (VEGF). Our results show that, after 7 days of treatment, all tested proteins change their pattern expression and will reset after 30 days. These data demonstrate that the dental pulp does not involve any irreversible iatrogenic alterations, supporting the efficacy and safety of using pre-calibrated force application to induce orthodontic tooth movement in clinical practice.

Discomalleolar ligament represents the vestiges of the primitive lateral pterygoid muscle which penetrates in the caudal end of Meckel's cartilage; during the development of newborn, the petrotympanic fissure close almost completely leaving inside the discomalleolar ligament. After entering in tympanic cavity, some fibers of the discomalleolar ligament insert to walls of cavity, other fibers continue with the lateral margin of the anterior ligament and insert in the neck of malleus; in contrast, other Authors demonstrated that discomalleolar ligament is an independent structure inserted in proximity of the neck of the malleus. Although the discomalleolar ligament can be considered as a structure of clinical importance, it is not described by anatomy textbooks. Moreover, it is likely that important correlations between temporomandibular diseases and otological symptoms exist. We have studied discomalleolar ligament submitting the specimens to the 3D volume rendering technique, light microscopy, reconstructing a wide light microscopic fields to analyze the real connection between retrodiscal connective tissue and middle ear, and immunofluorescence methods in order to analyze the consistence of ligament. We have shown two types of connections between TMJ and ear: first, with external acoustic meatus and, second, with middle ear through discomalleolar ligament. The different insertion represents a strong support in order to demonstrate that the TMJ disorders can determine variations of tension that are transmitted on the tympanic membrane provoking tinnitus in according to clinical features. Then, we propose that it is necessary to mention, also in anatomy textbook, the discomalleolar ligament as ligament distance of TMJ., (© 2020 The Authors.)

The aim of this study was to evaluate the correlation between marginal gingivitis, oral hygiene parameters, and interleukin-6 (IL-6) levels in gingival crevicular fluid of 40 children. The marginal periodontal pathology was evaluated by gingival index (GI). The status of oral hygiene was estimated by using patient hygiene performance (PHP), brushing frequency (BF), and plaque index (PI). IL-6 levels in gingival crevicular fluid were measured to evaluate the inflammation in marginal gingiva. PHP score showed a significant correlation with GI, BF, and PI. The groups based on PHP ranges were significantly related to IL-6 concentration in crevicular fluid.

Aim: To critically analyse the management of status dystonicus and prestatus dystonicus in children and adolescents, in order to examine clinical features, acute management, and risk of relapse in a paediatric cohort., Method: Clinical, demographic, and therapeutic features were analysed according to disease severity. Risk of subsequent relapse was estimated through Kaplan-Meier curves., Results: Thirty-four patients (eight females, 26 males) experiencing 63 episodes of acute dystonia exacerbations at a tertiary referral Italian hospital were identified. Mean age at status dystonicus presentation was 9 years 11 months (11y at inclusion in the study). Onset of dystonia dated back to infancy in most cases. Fourteen patients experienced two or more episodes. Infections were the most common trigger (48%). Benzodiazepines were the most commonly used drugs for acute management. Stereotactic pallidotomy was performed in six cases during status dystonicus, and in two additional patients it was electively performed after medical management. The probability of survival free from status dystonicus relapses was 78% after 4 months and 61% after 27 months., Interpretation: Dystonia exacerbations are potentially life-threating emergencies, with a considerable risk of relapse. Nevertheless, no obvious factors for relapse risk stratification exist. Pallidotomy is a feasible option in medical refractory status dystonicus for patients with limited deep brain stimulation applicability, but the risk of recurrence is elevated., What This Paper Adds: Acute exacerbations may affect up to 10% of children with dystonia. Infections are the most common precipitant factor. In about 30% of the cases, intensive care unit admission is needed. Subsequent relapses are common, reaching 25% risk at 1 year. Pallidotomy can be considered in medical-refractory cases with no deep brain stimulation applicability., (© 2019 Mac Keith Press.)

Paroxysmal movement disorders (PMDs) are rare neurological diseases typically manifesting with intermittent attacks of abnormal involuntary movements. Two main categories of PMDs are recognized based on the phenomenology: Paroxysmal dyskinesias (PxDs) are characterized by transient episodes hyperkinetic movement disorders, while attacks of cerebellar dysfunction are the hallmark of episodic ataxias (EAs). From an etiological point of view, both primary (genetic) and secondary (acquired) causes of PMDs are known. Recognition and diagnosis of PMDs is based on personal and familial medical history, physical examination, detailed reconstruction of ictal phenomenology, neuroimaging, and genetic analysis. Neurophysiological or laboratory tests are reserved for selected cases. Genetic knowledge of PMDs has been largely incremented by the advent of next generation sequencing (NGS) methodologies. The wide number of genes involved in the pathogenesis of PMDs reflects a high complexity of molecular bases of neurotransmission in cerebellar and basal ganglia circuits. In consideration of the broad genetic and phenotypic heterogeneity, a NGS approach by targeted panel for movement disorders, clinical or whole exome sequencing should be preferred, whenever possible, to a single gene approach, in order to increase diagnostic rate. This review is focused on clinical and genetic features of PMDs with the aim to (1) help clinicians to recognize, diagnose and treat patients with PMDs as well as to (2) provide an overview of genes and molecular mechanisms underlying these intriguing neurogenetic disorders., Competing Interests: The authors declare no conflict of interest.

Dominant mutations in ATP1A1, encoding the alpha-1 isoform of the Na + /K + -ATPase, have been recently reported to cause an axonal to intermediate type of Charcot-Marie-Tooth disease (ie, CMT2DD) and a syndrome with hypomagnesemia, intractable seizures and severe intellectual disability. Here, we describe the first case of hereditary spastic paraplegia (HSP) caused by a novel de novo (p.L337P) variant in ATP1A1. We provide evidence for the causative role of this variant with functional and homology modeling studies. This finding expands the phenotypic spectrum of the ATP1A1-related disorders, adds a piece to the larger genetic puzzle of HSP, and increases knowledge on the molecular mechanisms underlying inherited axonopathies (ie, CMT and HSP)., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Tubulinopathies are rare neurological disorders caused by alterations in tubulin structure and function, giving rise to a wide range of brain abnormalities involving neuronal proliferation, migration, differentiation and axon guidance. TUBB is one of the ten β-tubulin encoding genes present in the human genome and is broadly expressed in the developing central nervous system and the skin. Mutations in TUBB are responsible for two distinct pathological conditions: the first is characterized by microcephaly and complex structural brain malformations and the second, also known as "circumferential skin creases Kunze type" (CSC-KT), is associated to neurological features, excess skin folding and growth retardation. We used a combination of immunocytochemical and cellular approaches to explore, on patients' derived fibroblasts, the functional consequences of two TUBB variants: the novel mutation (p.N52S), associated with basal ganglia and cerebellar dysgenesis, and the previously reported variant (p.M73T), linked to microcephaly, corpus callosum agenesis and CSC-KT skin phenotype. Our results demonstrate that these variants impair microtubule (MT) function and dynamics. Most importantly, our studies show an altered epidermal growth factor (EGF) and transferrin (Tf) intracellular vesicle trafficking in both patients' fibroblasts, suggesting a specific role of TUBB in MT-dependent vesicular transport., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

This study evaluates salivary immunoglobulin A (s-IgA) and interleukin 6 (IL-6) in saliva of children and its correlation to tooth decay severity. Fifty-nine patients were divided into two groups: caries free (A group) and caries active (B group). B group was investigated according to Mount and Monse indices. Mean salivary IgA rate between two groups (A 16.7 ± 4.5 mg/dL vs. B 21.8 ± 12.9 mg/dL) was not significant, while IL-6 rate (A 19.02 ± 5.3 pg/mL vs. B 30.2 ± 11.8 pg/mL) was statistically different. This study revealed that salivary IL-6 levels were significantly higher in children with active caries when compared with the caries-free group, while the s-IgA rate showed no significant differences between the two groups.

Recessive mutations in DDHD2 cause SPG54, a complex hereditary spastic paraplegia (HSP) with less than forty patients reported worldwide. In this retrospective, multicenter study we describe eight additional SPG54 cases harboring homozygous or compound heterozygous DDHD2 variants. Finally, we reviewed literature data on SPG54, with the aim to better define the phenotype and the brain magnetic resonance imaging (MRI) pattern as well as genotype-phenotype correlations. SPG54 is typically characterized by early-onset (i.e., congenital or, more frequently, infantile) delay in motor and cognitive milestones, coupled or followed by appearance of spasticity. Cognitive impairment is absent in adult-onset cases. Spasticity progresses over time. Abnormal eye movement, found in about 50% of cases, is the feature most frequently associated with spasticity and developmental delay. Cerebellar ataxia is a prominent sign in several patients, including one adult of this study, suggesting to include SPG54 in the differential diagnosis of spastic-ataxia syndromes. Brain MRI shows thin corpus callosum and non-specific periventricular white matter lesions in about 90% and 70% of cases, respectively. Brain MR spectroscopy reveals abnormal lipid peak in 90% of investigated patients. Twenty-one pathogenic changes have been reported so far, many of which are nonsense or small deletion/duplication. Most mutations appear to be private, with only two mutations recurring in three (i.e., R287*) or more families (i.e., D660H). The identification of nine novel variants expands the molecular spectrum of DDHD2-related HSP and corroborates the notion of a quite homogeneous clinical and neuroradiological phenotype in spite of different genotypes.

The periodontal ligament (PDL) is a highly vascularized connective tissue surrounding the root of a tooth. In particular, the PDL is continuously exposed to mechanical stresses during the phases of mastication, and it provides physical, sensory, and trophic functions. It is known that the application of orthodontic force creates a change in periodontal structures. In fact, these forces generate a pressure on the ligament that closes the vessels. The aim of this study is to observe the modifications of vascular endothelial growth factor (VEGF) in the PDL and extracellular matrix proteins after application of a pre-calibrated and constant orthodontic force at different phases of treatment. We used a 50-g NiTi coiled spring and in vivo samples of PDL of maxillary and mandibular premolars of patients subjected to orthodontic treatment. These teeth were extracted at 1, 7, 14, 21, and 30 days, respectively, by application of force. The extraction of the PDL was effectuated by scarifying the radicular surface on the pressure and tension sides. The mechanical stress induced by the application of force caused an increase in the reactive type of metabolism of extracellular matrix proteins and modulation of neoangiogenesis until restoration., (© 2019 The Authors. Published by Elsevier Ltd.)

Heterozygous missense variants in the SPTBN2 gene, encoding the non-erythrocytic beta spectrin 2 subunit (beta-III spectrin), have been identified in autosomal dominant spinocerebellar ataxia type 5 (SCA5), a rare adult-onset neurodegenerative disorder characterized by progressive cerebellar ataxia, whereas homozygous loss of function variants in SPTBN2 have been associated with early onset cerebellar ataxia and global developmental delay (SCAR14). Recently, heterozygous SPTBN2 missense variants have been identified in a few patients with an early-onset ataxic phenotype. We report five patients with non-progressive congenital ataxia and psychomotor delay, 4/5 harboring novel heterozygous missense variants in SPTBN2 and one patient with compound heterozygous SPTBN2 variants. With an overall prevalence of 5% in our cohort of unrelated patients screened by targeted next-generation sequencing (NGS) for congenital or early-onset cerebellar ataxia, this study indicates that both dominant and recessive mutations of SPTBN2 together with CACNA1A and ITPR1, are a frequent cause of early-onset/congenital non-progressive ataxia and that their screening should be implemented in this subgroup of disorders., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of this study was to investigate the mechanical properties of a fiber hollow endodontic post characterized by the presence of an empty central cylindrical channel extended along the whole length. This particular shape allows clinicians to use the post also as a cementation resin carrier. Ten hollow posts were divided in two groups: the control group (unfilled hollow posts) (Group 0) and hollow posts filled with dual resin cement (Group 1). The samples of both groups were subjected to mechanical and micromorphological analysis by performing a three-point test and SEM observations. In the three-point test, the Group 1 samples exhibited a fracture load of 57.09 ± 5.06 N, a flexural strength of 1323.53 ± 110.09 MPa, and a Young's modulus of 42.87 ± 0.86 GPa. The samples of Group 2 exhibited a fracture load of 38.17 ± 1.7 N, a flexural strength of 908.87 ± 30.98 MPa, and a Young's modulus of 40.33 ± 1.9 GPa. The difference between fracture load, flexural strength, and deflection between the two groups was statistically highly significant ( p < 0.01). Further, the difference between the Young's modulus of the two groups was statistically significant ( p < 0.05). The values obtained are similar to those of other posts available on the market.

SLC2A1 mutations cause glucose transporter type 1 deficiency syndrome, whose phenotypic spectrum is a continuum, ranging from classic to variant phenotypes, the latter accounting for about 10% of cases. Very few SLC2A1-mutated patients with a spastic paraplegia phenotype have been reported so far, and they are associated with paroxysmal choreo-athetosis (i.e., DYT9). The authors describe two sporadic children with pure and complex hereditary spastic paraplegia (HSP) without paroxysmal non-epileptic movement disorders harboring heterozygous de novo SLC2A1 pathogenic variants. These patients have been identified by a targeted panel for HSP among 140 pediatric- and adult-onset unrelated cases with pure and complex HSP, thus indicating an overall prevalence of 1.4% of SLC2A1 mutations, which increases to 3% if only pediatric-onset patients are considered. The implications of these findings in the diagnostic work-up of HSP patients are discussed., (Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: A radiological evaluation is essential in endodontics, for diagnostic purposes, planning and execution of the treatment, and evaluation of the success of therapy. The periapical radiography is nowadays the main radiographic investigations used but presents some limits as 3D anatomic alteration, geometric compression, and possible anatomical structures overlapping that can obscure the area of interest. CBCT (cone beam computed tomography) in endodontics allows a detailed assessment of the teeth and surrounding alveolar anatomy for endodontic diagnosis, treatment planning, and follow-up., Objective: The purpose of this study was to evaluate the accuracy of CBCT in comparison with conventional intraoral radiographs used in endodontic procedures., Materials and Methods: Statistical analysis was performed on 101 patients with previous endodontic treatments with the relative radiographic documentation (preoperative, postoperative, and follow-up intraoral X-ray) that had underwent at CBCT screening for surgical reasons. The CBCT scans were evaluated independently by two operators and compared with the corresponding periapical images., Results: Our analysis shows that the two radiological investigations statistically agree in 100% of cases in the group of patients without any endodontic sign. In the group of patients with an endodontic pathology, detected with CBCT, endodontic under extended treatments (30.6%), MB2 canals in nontreated maxillary molars (20.7%), second canals in nontreated mandibular incisors (9%), root fractures (2.7%), and root resorption (2.7%) were not always visible in intraoral X-ray. Otherwise, positivity in the intraoral X-ray was always confirmed in CBCT. A radiolucent area was detected in CBCT exam in 46%, while the intraoral X-ray exam was positive only in 18%., Conclusions: Our study shows that some important radiological signs acquired using CBCT are not always visible in periapical X-ray. Furthermore, CBCT is considered as a II level exam and could be used to solve diagnostic questions, essential to a proper management of the endodontic problems.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

ATP1A3 mutations are related to a wide spectrum of clinical conditions, including several defined syndromes as rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS), together with many other intermediate phenotypes. Ataxia is always more increasingly reported, either as accessory or prominent sign, in ATP1A3-related conditions, being thus considered as a peculiar feature of this spectrum. Here, we report three cases of childhood rapid-onset ataxia due to two different ATP1A3 variants. Interestingly, two patients (mother and son) showed a variant c.2266C>T (p.R756C), while the third carried the c.2452G>A (p.E818K) variant, commonly described in association with CAPOS syndrome. Our report contributes to extent the phenotypic spectrum of ATP1A3 mutations, remarking childhood rapid-onset ataxia as an additional clinical presentation of ATP1A3-related conditions. Finally, we discussed this phenomenology in the light of translational evidence from a RDP animal model.

Mutations in KCNJ10, which encodes the inwardly rectifying potassium channel Kir4.1, a primary regulator of membrane excitability and potassium homeostasis, cause a complex syndrome characterized by seizures, sensorineural deafness, ataxia, intellectual disability, and electrolyte imbalance called SeSAME/EAST syndrome. We describe a 41-year-old patient with non-syndromic, slowly progressive, early-onset ataxia. Targeted next-generation sequencing identified a novel c.180 T > G (p.Ile60Met) missense homozygous mutation. The mutated residue Ile60Met likely impairs phosphatidylinositol 4, 5-bisphosphate (PIP2) binding which is known to play an essential role in channel gating. Our study expands the clinical and mutational spectrum of KCNJ10-related disorders and suggests that screening of this gene should be implemented in patients with early-onset ataxia, with or without syndromic features.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurological disorders characterized primarily by a pyramidal syndrome with lower limb spasticity, which can manifest as pure HSP or associated with a number of neurological or non-neurological signs (i.e., complicated HSPs). The clinical variability of HSPs is associated with a wide genetic heterogeneity, with more than eighty causative genes known. Recently, next generation sequencing (NGS) has allowed increasing genetic definition in such a heterogeneous group of disorders. We report on a 56- year-old man affected by sporadic complicated HSP consisting of a pyramidal syndrome, cerebellar ataxia, congenital cataract, pes cavus, axonal sensory-motor peripheral neuropathy and cognitive decline. Brain MRI showed cerebellar atrophy and thin corpus callosum. By NGS we found a novel homozygous biallelic c.452-1G > C mutation in the b-glucosidase 2 gene (GBA2), known to be causative for autosomal recessive hereditary spastic paraplegia type 46 (SPG46). The rarity of this inherited form besides reporting on a novel mutation, expands the genetic and clinical spectrum of SPG46 related HSP., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Alternating Hemiplegia of Childhood (AHC) is a rare neurological disease caused by mutations in ATP1A3 gene codifying for alpha3 subunit of Na + -K + ATPase pump. Repeated and transient attacks of hemiplegia, usually affecting one side of the body or the other, or both sides of the body at once, are the core features of AHC. Monocular nystagmus, other abnormalities in ocular movements, dystonic posturing and epilepsy are commonly associated to AHC. However, the spectrum of ATP1A3 related diseases is still expanding and new phenotypes have been reported., Case Report: Here, we described a patient who developed a severe early onset drug-resistant epileptic encephalopathy and months later, he presented episodes of hemiplegic attacks and monocular nystagmus. Thus, AHC was hypothesized and a novel mutation in ATP1A3 gene was found. Interestingly, ketogenic diet (KD) was started and both epileptic seizures and classical AHC paroxysmal episodes stopped. Long-term follow-up shows a global improvement of neurological development., Conclusions: Our case reinforces the role of KD as a novel therapeutic option for ATP1A3-related conditions. However, proper dedicated confirmatory trials on KD are necessary., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Hereditary spastic paraplegias (HSP) are clinical and genetic heterogeneous diseases with more than 80 disease genes identified thus far. Studies on large cohorts of HSP patients showed that, by means of current technologies, the percentage of genetically solved cases is close to 50%. Notably, the percentage of molecularly confirmed diagnoses decreases significantly in sporadic patients. To describe our diagnostic molecular genetic approach on patients with pediatric-onset pure and complex HSP, 47 subjects with HSP underwent molecular screening of 113 known and candidate disease genes by targeted capture and massively parallel sequencing. Negative cases were successively analyzed by multiplex ligation-dependent probe amplification (MLPA) analysis for the SPAST gene and high-resolution SNP array analysis for genome-wide CNV detection. Diagnosis was molecularly confirmed in 29 out of 47 (62%) patients, most of whom had clinical diagnosis of cHSP. Although SPG11 and SPG4 remain the most frequent cause of, respectively, complex and pure HSP, a large number of pathogenic variants were disclosed in POLR3A, FA2H, DDHD2, ATP2B4, ENTPD1, ERLIN2, CAPN1, ALS2, ADAR1, RNASEH2B, TUBB4A, ATL1, and KIF1A. In a subset of these disease genes, phenotypic expansion and novel genotype-phenotype correlations were recognized. Notably, SNP array analysis did not provide any significant contribution in increasing the diagnostic yield. Our findings document the high diagnostic yield of targeted sequencing for patients with pediatric-onset, complex, and pure HSP. MLPA for SPAST and SNP array should be limited to properly selected cases based on clinical suspicion.

Background: The INI1/SMARCB1 gene protein product has been implicated in the direct pathogenesis of schwannomas from patients with one form of schwannomatosis [SWNTS1; MIM # 162091] showing a mosaic pattern of loss of protein expression by immunohistochemistry [93% in familial vs. 55% in sporadic cases]., Aim of Study: To verify whether such INI1/SMARCB1 mosaic pattern could be extended to all schwannomas arising in the sporadic and familial schwannomatoses [i.e. to SMARCB1-related (SWNTS1) or LZTR1-related (SWNTS2) schwannomatosis or to SMARCB1/LZTR1-negative schwannomatosis] and whether it could be involved in classical NF2 or solitary peripheral schwannomas METHODS: We blindly analysed schwannoma samples obtained from a total of 22 patients including (a) 2 patients (2 males; aged 38 and 55 years) affected by non-familial SMARCB1-associated schwannomatosis (SWTNS1); (b) 1 patient (1 female; aged 33 years) affected by familial schwannomatosis (SWTNS1/ SMARCB1 germ line mutations); (c) 5 patients (3 males, 2 females; aged 33 to 35 years) affected by non-familial (sporadic) LZTR1-associated schwannomatosis (SWNTS2); (d) 3 patients (3 males; aged 35 to 47 years) affected by familial schwannomatosis (SWTNS2/ LZTR1 germ line mutations); (e) 2 patients (1 male, 1 female; aged 63 and 49 years, respectively) affected by non-familial schwannomatosis (SWTNS, negative for SMARCB1, LZTR1 and NF2 gene mutations); (f) 4 patients (3 males, 1 females; aged 15 to 24 years) affected by classical NF2 (NF2: harbouring NF2 germ line mutations; and (g) 5 patients (3 males, 2 females; aged 33 to 68 years) who had solitary schwannomas. [follow-up = 15-30 years; negative for constitutional/somatic mutation analysis for the SMARCB1, LZTR1 and NF2 genes] were (blindly) analyzed. The INI1/SMARCB1 immunostaining pattern was regarded as (1) diffuse positive nuclear staining [= retained expression] or (2) mosaic pattern [mixed positive/negative nuclei = loss of expression in a subset of tumour cells]., Results: All solitary peripheral schwannomas and NF2-associated vestibular schwannomas showed diffuse nuclear INI1/SMARCB1 staining in 97-100% of neoplastic cells; schwannomas obtained from all cases of non-familial and familial schwannomatosis and NF2-associated non-vestibular schwannomas showed a mosaic pattern ranging from 10 to 70% of INI1/SMARCB1-positive expression. We did not record a complete lack of nuclear staining., Conclusions: The present data suggests that (a) mosaic loss of immunohistochemical INI1/SMARCB1 expression, despite the interlesional variability, is a reliable marker of schwannomatosis regardless of the involved gene and it might help in the differential diagnosis of schwannomatosis vs. solitary schwannomas and (b) INI1/SMARCB1 expression is not useful in the differential with mosaic NF2, since NF2-associated peripheral schwannomas show the same immunohistochemical pattern.

Post-operative pediatric cerebellar mutism syndrome (PPCMS) is a clinical syndrome arising from cerebellar injury and characterized by absence of speech and other possible symptoms and signs. Rare reports described some benefit after administration of dopamine agonist therapy, but no treatment has proven efficacy. In this paper, we report on the dramatic, sudden resolution of PPCMS induced by midazolam administration in a boy who underwent posterior fossa surgery for choroid plexus papilloma of the fourth ventricle. In addition to clinical improvement, post-midazolam single-photon emission computed tomography also demonstrated amelioration of brain perfusion.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents, due to the increased worldwide incidence of obesity among children. It is now clear enough that of diet high in carbohydrates and simple sugars are associated with hepatic steatosis and non-alcoholic steatohepatitis (NASH). Several studies have shown that an increased consumption of simple sugars is also positively associated with overweight and obesity, and related co-morbidities, such as type 2 diabetes, metabolic syndrome and NAFLD. It is difficult to define the role of the various components of soft drinks and energy drinks in the pathogenesis of NAFLD and its progression in NASH, but the major role is played by high calorie and high sugar consumption, mainly fructose. In addition, other components of these beverages (e.g. xanthine) seem to have an important role in the pathogenesis of metabolic disorders, crucial pathways involved in NAFLD/NASH. The drastic reduction in the consumption of energy drinks and soft drinks is an appropriate intervention for the prevention of obesity and NAFLD in young people.

Purpose: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions., Patients and Methods: This Italian multicenter retrospective observational study was performed in 16 paediatric epilepsy centres. Inclusion criteria were: (i) ≤18 years of age, (ii) history of refractory epilepsy, (iii) a follow-up ≥5 months of PER add-on therapy. Exclusion criteria were: (i) a diagnosis of primary idiopathic generalized epilepsy, (ii) variation of concomitant AEDs during the previous 4 weeks. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline., Results: 62 patients suffering from various refractory epilepsies were included in this study: 53% were males, the mean age was 14.2 years (range 6-18 years), 8 patients aged <12 years. Mean age at epilepsy onset was 3.4 years and the mean duration of epilepsy was 10.8 years (range 1-16), which ranged from 2 seizures per-month up to several seizures per-day (mean number=96.5). Symptomatic focal epilepsy was reported in 62.9% of cases. Mean number of AEDs used in the past was 7.1; mean number of concomitant AEDs was 2.48, with carbamazepine used in 43.5% of patients. Mean PER daily dose was 7.1mg (2-12mg). After an average of 6.6 months of follow-up (5-13 months), the retention rate was 77.4% (48/62). The response rate was 50%; 16% of patients achieved ≥75% seizure frequency reduction and 5% became completely seizure free. Seizure aggravation was observed in 9.7% of patients. Adverse events were reported in 19 patients (30.6%) and led to PER discontinuation in 4 patients (6.5%). The most common adverse events were behaviour disturbance (irritability and aggressiveness), dizziness, sedation and fatigue., Conclusion: PER was found to be a safe and effective treatment when used as adjunctive therapy in paediatric patients with uncontrolled epilepsy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The association between migraine and stroke is still a dilemma for neurologists. Migraine is associated with an increased stroke risk and it is considered an independent risk factor for ischaemic stroke in a particular subgroup of patients. The pathogenesis is still unknown even if several studies report some common biochemical mechanisms between these two diseases. A classification of migraine-related stroke that encompasses the full spectrum of the possible relationship between migraine and stroke includes three main entities: coexisting stroke and migraine, stroke with clinical features of migraine, and migraine-induced stroke. The concept of migraine-induced stroke is well represented by migrainous infarction and it is described in the revised classification of the International Headache Society (IHS), representing the strongest demonstration of the relationship between ischaemic stroke and migraine. A very interesting common condition in stroke and migraine is patent foramen ovale (PFO) which could play a pathogenetic role in both disorders. The neuroradiological evidence of subclinical lesions most typical in the white matter and in the posterior artery territories in patients with migraine, opens a new field of research. In conclusion the association between migraine and stroke remains an open question. Solving the above mentioned issues is fundamental to understand the epidemiologic, pathogenetic and clinical aspects of migraine-related stroke.

Introduction: Studies on Mean Platelet Volume (MPV) in children with Sleep Disordered Breathing (SDB) report conflicting results and the hypothesis of an intermittent hypoxemia leading to a systemic inflammation is reaching consensus. Vitamin D exerts anti-inflammatory properties and its deficiency has been supposed to play a role in sleep disorders. Emerging interest is rising about Primary Snoring (PS) since it is reasonable that also undetectable alteration of hypoxia might predispose to an increased production of inflammatory mediators. In this perspective, in a group of children affected by SDB, our aim was to investigate MPV, vitamin D and C Reactive Protein (CRP) levels, which had been previously evaluated separately in different studies focused only on Obstructive Sleep Apnea Syndrome (OSAS)., Materials and Methods: We enrolled 137 children: 70 healthy controls (HC), 67 affected by SDB undergoing a polysomnographic evaluation, 22 with a diagnosis of PS and 45 with a diagnosis of OSAS. All patients underwent routine biochemical evaluations including blood cell counts, CRP and vitamin D., Results: Children affected by SDB had a mean age of 8.49±2.19 and were prevalently males (23 females, 34%; 44 males, 66%). MPV levels were higher in OSAS and PS when compared to HC; platelet count (PLT) and CRP levels were higher while Vitamin D levels were lower in children with SDB when compared to HC. MPV levels were correlated with PLT (r = -0.54; p<0.001), vitamin D (r = -0.39; p<0.001) and CRP (r = 0.21; p<0.01). A multiple regression was run to predict MPV levels from vitamin D, CRP and PLT and these variables significantly predicted MPV (F = 17.42, p<0.0001; adjusted R2 = 0.37). Only platelet count and vitamin D added statistically significantly to the prediction (p<0.05)., Conclusion: The present study provides evidence of higher MPV and lower vitamin D levels in children with PS as well as in children with OSAS, and supports the underlying inflammation, hence, highlighting the importance of an early diagnosis of this previously considered benign form of SDB.

Multidrug transporters (MDTs) are likely to play a role in the pathogenesis of drug resistance in epilepsy, acting at the level of the blood-brain barrier by returning antiepileptic drugs to the blood vessels and lowering brain penetration and concentration (e.g. the so-called multidrug transporter hypothesis). In the last ten years experimental studies on both animal models and human brain tissues have highlighted a potential role of the P-glycoprotein-one of the multidrug transporters of the blood-brain barrier-in the pathophysiology of drug-resistant epilepsies. At the same time, verapamil has been administered to patients with drug-resistant epilepsy (e.g., Dravet syndrome, Lennox-Gastaut syndrome, focal epilepsies) or status epilepticus with promising results. In this drug profile paper the authors review current knowledge and main published studies regarding the role of the L-type calcium channel antagonist verapamil in drug-resistant epilepsy.

Seizures are rarely reported in Williams-Beuren syndrome (WBS)--a contiguous-gene-deletion disorder caused by a 7q11.23 heterozygous deletion of 1.5-1.8 Mb--and no previous study evaluated electro-clinical features of epilepsy in this syndrome. Furthermore, it has been hypothesized that atypical deletion (e.g., larger than 1.8 Mb) may be responsible for a more pronounced neurological phenotypes, especially including seizures. Our objectives are to describe the electro-clinical features in WBS and to correlate the epileptic phenotype with deletion of the 7q11.23 critical region. We evaluate the electro-clinical features in one case of distal 7q11.23 deletion syndrome and in eight epileptic WBS (eWBS) patients. Additionally, we compare the deletion size-and deleted genes-of four epileptic WBS (eWBS) with that of four non-epileptic WBS (neWBS) patients. Infantile spasms, focal (e.g., motor and dyscognitive with autonomic features) and generalized (e.g., tonic-clonic, tonic, clonic, myoclonic) seizures were encountered. Drug-resistance was observed in one patient. Neuroimaging discovered one case of focal cortical dysplasia, one case of fronto-temporal cortical atrophy and one case of periventricular nodular heterotopia. Comparison of deletion size between eWBS and neWBS patients did not reveal candidate genes potentially underlying epilepsy. This is the largest series describing electro-clinical features of epilepsy in WBS. In WBS, epilepsy should be considered both in case of typical and atypical deletions, which do not involve HIP1, YWHAG or MAGI2., (© 2015 Wiley Periodicals, Inc.)

Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder characterized by early onset encephalopathy, chronic diarrhoea, petechiae, orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected in body fluids. EE is caused by mutations in ETHE1 gene, a mitochondrial sulfur dioxygenase. Neurologic signs and symptoms include progressively delayed development, hypotonia, seizures, and abnormal movements. We report on the clinical, electroencephalographic and MRI findings of a baby with a severe early onset encephalopathy associated with novel ETHE1 gene mutation. This is the first case described in literature with an early pure epileptic onset, presenting with West syndrome.

Background: To evaluate evidence and prognosis of refractory cases of absence seizures., Methods: Subjects with refractory absence seizures were identified retrospectively in 17 Italian epilepsy pediatrics Centers. We analyzed age at onset, family history, presence of myoclonic components, seizure frequency, treatment with antiepileptic drugs (AEDs), interictal electroencephalography (EEG) and neuropsychological assessment. Two subgroups were identified: one with patients with current absence seizures and another with patients that had become seizure free with or without AED treatment. The chi-square test was applied., Results: A total of 92 subjects with drug-resistant absence seizures were analyzed. 45 subjects still show absence seizures (49%) and the other 47 became seizure free (51%) after a period of drug-resistance. The statistical analysis between these two groups showed no correlation between age of onset, family history and abnormalities at interictal EEG. Statistically significant differences were observed with regard to the number of AEDs used and intellectual disability., Conclusion: Typical absence epilepsy classifiable as Childhood Absence Epilepsy could not be considered so "benign", as suggested in literature. A longer duration of disease and a higher frequency of seizure seem to be correlated with a higher presence of cognitive impairment. No significant risk factor was observed to allow the faster and better recognition of patients with worse prognosis., (Copyright © 2015. Published by Elsevier Ltd.)

Deletions in the 9q33-q34 region have been reported in patients with early onset epileptic encephalopathy, but a consistent phenotype has yet to emerge. We report on the diagnosis of a de novo 9q33-q34.12 microdeletion of 4 Mb in a 15-month-old girl presenting with severe psychomotor delay, facial dysmorphisms, thin corpus callosum and early myoclonic encephalopathy. This deletion encompasses 101 RefSeq genes, including the four autosomal dominant genes STXBP1, SPTAN1, ENG and TOR1A. We discuss genetic, clinical and epileptic features comparing our patient with those previously reported in the literature., (© 2015 John Wiley & Sons Ltd/University College London.)

Spinal neurofibromatosis (SNF) is a related form of neurofibromatosis 1 (NF1), characterized by bilateral neurofibromas (histologically proven) of all spinal roots (and, eventually, of all the major peripheral nerve branches) with or without other manifestations of classical NF1. By rigorous application of these criteria to the 98 SNF cases published, we developed: (i) a cohort of 49 SNF patients (21 males and 28 females; aged 4-74 years]: 9 SNF families (21/49), 1 mixed SNF/NF1 family (1/49) and 27 of 49 sporadic SNF patients (including 5 unpublished patients in this report); and (ii) a group of 49 non-SNF patients including: (a) 32 patients with neurofibromas of multiple but not all spinal roots (MNFSR): 4 mixed SNF/MNFSR families (6/32); (b) 14 patients with NF1 manifestations without spinal neurofibromas, belonging to SNF (8/49) or MNFSR families (6/32); (c) 3 patients with neurofibromas in one spinal root. In addition to reduced incidence of café-au-lait spots (67% in SNF vs 56% in MNFSR), other NF1 manifestations were less frequent in either cohort. Molecular testing showed common NF1 gene abnormalities in both groups. The risk of developing SNF vs NF1 was increased for missense mutations [p = 0.0001; odds ratio (OR) = 6.16; confidence interval (CI) = 3.14-13.11], which were more frequent in SNF vs MNFSR (p = 0.0271)., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Myoclonic status in nonprogressive encephalopathy (MSNE) is an early-onset, drug-resistant epileptic syndrome characterized by occurrence of continuous diffuse epileptiform abnormalities, associated with positive and/or negative phenomena and accompanied by transient and recurring motor, cognitive, and behavioral impairment. MSNE has been reported in Angelman syndrome (AS) secondary to 15q11-13 deletions or UBE3A mutations but not to paternal uniparental disomy (UPD). We describe the case of a male patient with AS caused by UPD who developed a myoclonic status (MS) associated with long-lasting fever of central origin, both promptly regressed with introduction of levetiracetam. Only three descriptions of thermal dysregulation in AS exist, and none of the previously reported cases were associated with MS or with UPD. Association of MS and central fever expands the spectrum of epileptic and non-epileptic features in UPD-related AS and provides a further evidence of hypothalamus involvement in the pathogenesis of this neurodevelopmental disorder.

Objective: Epilepsy in Ehlers-Danlos syndrome (EDS) has been reported in the literature, but there are no studies that have investigated in detail clinical and electroencephalography (EEG) features in patients with EDS, and that have compared the outcome of epilepsy in subjects with or without brain lesions. We report a series of 42 patients with EDS and epilepsy, including data that concern clinical characteristics, EEG abnormalities, brain malformations at magnetic resonance imaging (MRI) and long-term outcome., Methods: EEG, clinical information, and neuroimaging characteristics in 42 patients with EDS were analyzed at the onset of epilepsy and after long-term follow-up (at least 5 years). We subdivided the patients into two groups: group A, 26 patients without brain abnormalities; group B, 16 patients with brain lesions, often with periventricular heterotopia (PH)., Results: Group A patients: Most cases (19 of 26) presented focal epilepsy, whereas 7 of 26 were affected by generalized epilepsy; interictal EEG showed temporal or temporoparietal spikes in most cases. Twenty-three patients received antiepileptic drug (AED) monotherapy; three patients were treated with polytherapy. During follow-up, all patients were seizure-free for at least 2 years, and only one continued to receive AEDs. Group B patients: the majority presented focal epilepsy (9 of 16), but many patients had generalized epilepsy (7 of 16); interictal EEG showed usually frontal or frontotemporal spikes and waves. Many patients (12 of 16) received AED polytherapy. During follow-up, 12 patients were seizure-free, and all patients continued pharmacologic treatment., Significance: All patients without brain lesions showed a favorable response to AED monotherapy and were seizure-free after a few years of treatment. Patients with central nervous system abnormalities had a worse outcome, suggesting that the presence of brain lesions could influence the long-term evolution in these patients., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS.

Seizures are observed with a frequency of 3-21% in children with fetal alcohol spectrum disorders (FASD). However, clinical, neuroradiologic, and electroencephalography (EEG) features are poorly described. In this study, 13 patients with FASD and epilepsy or seizures were identified retrospectively from the databases of seven Italian pediatric neurology divisions. Eleven children were affected by epilepsy, and two had at least one documented seizure. Both generalized and focal seizures were observed. EEG showed diffuse or focal epileptic activity; two children developed electric status epilepticus during sleep (ESES). Structural brain anomalies, including polymicrogyria, nodular heterotopia, atrophy, and Arnold-Chiari type 1 malformation, were discovered in almost 50% of patients. Control of seizures was not difficult to obtain in 11 cases; one patient showed pharmacoresistant epilepsy. EEG and clinical follow-up are recommended in children with FASD and epilepsy, since severe conditions requiring aggressive treatment, such as in ESES, may develop. Neuroradiological evaluation is warranted because several types of brain anomalies could be associated with maternal alcohol consumption during pregnancy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)