Abstract The current spectrum of disorders associated to clinical spasms with onset in infancy is wider than previously thought; accordingly, its terminology has changed. Nowadays, the term Infantile ...spasms syndrome ( ISs ) defines an epileptic syndrome occurring in children younger than 1 year (rarely older than 2 years), with clinical (epileptic: i.e., associated to an epileptiform EEG) spasms usually occurring in clusters whose most characteristic EEG finding is hypsarrhythmia the spasms are often associated with developmental arrest or regression. The term West syndrome ( WS ) refers to a form (a subset) of ISs, characterised by the combination of clustered spasms and hypsarrhythmia on an EEG and delayed brain development or regression currently, it is no longer required that delayed development occur before the onset of spasms. Less usually, spasms may occur singly rather than in clusters infantile spasms single-spasm variant ( ISSV ), hypsarrhythmia can be (incidentally) recorded without any evidence of clinical spasms hypsarrhythmia without infantile spasms ( HWIS ) or typical clinical spasms may manifest in absence of hypsarrhythmia infantile spasms without hypsarrhythmia (I SW) . There is a growing evidence that ISs and related phenotypes may result, besides from acquired events, from disturbances in key genetic pathways of brain development: specifically, in the gene regulatory network of GABAergic forebrain dorsal–ventral development, and abnormalities in molecules expressed at the synapse. Children with these genetic associations also have phenotypes beyond epilepsy, including dysmorphic features, autism, movement disorders and systemic malformations. The prognosis depends on: (a) the cause, which gives origin to the attacks (the complex malformation forms being more severe); (b) the EEG pattern(s); (c) the appearance of seizures prior to the spasms; and (d) the rapid response to treatment. Currently, the first-line treatment includes the adrenocorticotropic hormone ACTH and vigabatrin. In the near future the gold standard could be the development of new therapies that target specific pathways of pathogenesis. In this article we review the past and growing number of clinical, genetic, molecular and therapeutic discoveries on this expanding topic.
Due to potentially harmful exposure to X-rays, condylar growth in response to orthodontic treatment is poorly studied. To overcome this limitation, here, the authors have proposed high-resolution MRI ...as a viable alternative to CBCT for clinical 3D assessment of TMJ. A male subject underwent both MRI and CBCT scans. The obtained three-dimensional reconstructions of the TMJ were segmented and superimposed by a semiautomatic algorithm developed in MATLAB R2022a. The condylar geometries were reconstructed using dedicated software for image segmentation. Two geometrical parameters, i.e., the total volume and surface of the single condyle model, were selected to quantify the intraclass and interclass variability from the mean of each DICOM series (CBCT and MRI). The final comparison between the reference standard model of CBCT and 3T MRI showed that the former was more robust in terms of reproducibility, while the latter reached a higher standard deviation compared to CBCT, but these values were similar between the operators and clinically not significant. Within the inherent limitation of image reconstruction on MRI scans due to the current lower resolution of this technique, the method proposed here could be considered as a nucleus for developing future completely automatic AI algorithms, owing to its great potential and satisfactory consistency among different times and operators.
This work investigated whether the anti-resorptive drugs (ARDs) zoledronic acid (Zol) and denosumab (Dmab) affect differently the levels of circulating immune cell subsets, possibly predicting the ...risk of developing medication-related ONJ (MRONJ) during the first 18 months of treatment. Blood samples were collected from 10 bone metastatic breast cancer patients receiving cyclin inhibitors at 0, 6, 12, and 18 months from the beginning of Dmab or Zol treatment. Eight breast cancer patients already diagnosed with MRONJ and treated with cyclin inhibitors and ARDs were in the control group. PBMCs were isolated; the trend of circulating immune subsets during the ARD treatment was monitored, and 12 pro-inflammatory cytokines were analyzed in sera using flow cytometry. In Dmab-treated patients, activated T cells were stable or increased, as were the levels of IL-12, TNF-α, GM-CSF, IL-5, and IL-10, sustaining them. In Zol-treated patients, CD8+T cells decreased, and the level of IFN-γ was undetectable. γδT cells were not altered in Dmab-treated patients, while they dramatically decreased in Zol-treated patients. In the MRONJ control group, Zol-ONJ patients showed a reduction in activated T cells and γδT cells compared to Dmab-ONJ patients. Dmab was less immunosuppressive than Zol, not affecting γδT cells and increasing activated T cells.
Hemi-hydranencephaly is a very rare condition characterized by complete or almost near-complete unilateral absence of the cortical cortex, which is filled by a sac of cerebrospinal fluid. Prenatal ...vascular disruption with occlusion of the carotid artery territories ipsilateral to the damaged brain is the presumed pathogenesis.We have selected nine cases that fit the clinical and pathologic characteristics of hemi-hydranencephaly, demonstrating that destruction of one hemisphere may be not always associated with severe neurologic impairment and may allow an almost normal life. This disorder is an example of a possible prenatal re-organization in which the right and left cerebral hemispheres present functional potentiality to make up the damaged brain.The cases reported in the literature are discussed, including a patient previously reported and followed-up for 10 years. A review of the cases is performed with an evaluation of the most important aspect of this rare and mysterious disorder.
Background There is no agreement on the prevalence, natural history and outcome of infantile spasms (IS) in neurofibromatosis type 1 (NF1). By contrast, its prevalence and outcome are well ...characterised in the setting of other neurocutaneous disorders (e.g. tuberous sclerosis). Materials and methods The aim of the present study was to try to establish a genotype-phenotype correlation in IS in the setting of NF1. A retrospective (years 1990-2000) and prospective (years 2000-2006) study in three paediatric centres in Italy were taken as referral populations for: (1) children with NF1 and (2) neurological problems in childhood. Results Ten NF1 patients have had IS. The calculated population-based: (1) prevalence of IS in NF1 (0.76%) was higher than the reported frequency of IS in the general population (0.02-0.05%) and (2) frequency of NF1 in the IS series in two out of three centres (0.62-0.90%) was lower than the estimated frequencies in the literature (1.5-3.0%). Patients had psychomotor delay preceding the spasms (50%), symmetrical spasms (50%), typical (80%) and modified (20%) hypsarrhythmia and foci of spikes and waves and a good response to corticosteroid treatment (50%). Outcome was good in 30%. Imaging revealed high-signal foci in atypical locations (sub-cortical and central brain regions). Deoxyribonucleic acid analysis revealed three novel NF1 gene mutations without genotype-phenotype correlation. Conclusion Even though the combination of IS and NF1 does not seem to be coincidental, it is certainly an unusual event in NF1--rarer than in other neurocutaneous disorders. Spasms in NF1 are not associated with specific genetic defects.
Abstract We describe an infant with cutaneous and leptomeningeal diffuse hemangiomata. Clinical facial anomalies were evident at birth. Routine transfontanellar ultrasonography revealed very diffuse ...leptomeningeal hemangioma. Magnetic resonance imaging during the first days of age confirmed vascular lesions. The patient was otherwise normal, and was monitored at ages 3.5, 9, and 18 months. Rapid resolution of the hemangioma occurred within 1 year. The infant did not present with persistent embryonic arteries, a posterior fossa, or other malformations typically reported in Pascual-Castroviejo type II syndrome. However, the characteristic skin color, leptomeningeal hemangioma, and rapid involution prompted the diagnosis of Pascual-Castroviejo II syndrome in its wider, benign spectrum.
Background: We report a study conducted in children and adolescents who are affected by primary headaches. The aim was to establish the most useful investigations for diagnosing headaches.
Methods: ...The current study involved 300 consecutively hospitalized children and adolescents selected according to the criteria of the second edition of the International Classification of Headache Disorders. The following examinations were performed in all patients: full ophthalmologic; brain magnetic resonance imaging (MRI); electroencephalography; echocardiogram; and electrocardiogram. Dental, otorhinolaryngology, echocardiography of the supra‐aortic trunks, abdominal ultrasound, and visual‐ and auditory‐evoked potentials were carried out in patients according to the clinical signs associated with headache.
Results: In a large number of cases routine laboratory analysis and neurophysiologic investigations were within the normal value when neurologic examination was normal. Electroencephalography, ophthalmologic studies and cerebral MRI are advisable as they can reveal precocious pathologic events, even in the absence of evident or alarming clinical signs.
Conclusion: As widely reported in the literature, most of these investigations may be of little clinical value, but the authors reasoned that electroencephalography, ophthalmologic investigations and a cerebral MRI may be noteworthy because such studies may reveal a precocious pathologic event which can change the prognostic value of the headache. In addition, negative results on cerebral MRI may relieve the anxiety of parents and in turn may positively influence the clinical course of headache in children and adolescents.
John M. Opitz, a towering figure in both stature and scientific achievement, left an indelible mark on the fields of genetics, pediatrics, and embryology. Born in 1935 in Hamburg to a Jewish family, ...Opitz's early life was marked by adversities. Despite these challenges, he pursued a remarkable career, immigrating to the United States at 15 years and becoming a renowned scientist in institutions like Iowa State University and the University of Wisconsin, where he made groundbreaking contributions to clinical genetics.BACKGROUNDJohn M. Opitz, a towering figure in both stature and scientific achievement, left an indelible mark on the fields of genetics, pediatrics, and embryology. Born in 1935 in Hamburg to a Jewish family, Opitz's early life was marked by adversities. Despite these challenges, he pursued a remarkable career, immigrating to the United States at 15 years and becoming a renowned scientist in institutions like Iowa State University and the University of Wisconsin, where he made groundbreaking contributions to clinical genetics.A testament to his compassionate nature, Opitz dedicated himself to understanding and treating rare genetic disorders, earning him eponymous recognition in several medical conditions. His impact extended beyond academia, as evidenced by his collaborative efforts with Sicilian universities to advance clinical genetics in Italy. Opitz's teaching style emphasized simplicity, empathy, and meticulous clinical examination, leaving an indelible mark on students and colleagues.MAIN BODYA testament to his compassionate nature, Opitz dedicated himself to understanding and treating rare genetic disorders, earning him eponymous recognition in several medical conditions. His impact extended beyond academia, as evidenced by his collaborative efforts with Sicilian universities to advance clinical genetics in Italy. Opitz's teaching style emphasized simplicity, empathy, and meticulous clinical examination, leaving an indelible mark on students and colleagues.John M. Opitz's towering intellect, compassionate demeanor, and profound impact on medicine and genetics made him a figure of enduring significance. His legacy lives on through the countless lives he touched, the knowledge he transmitted, and the enduring friendships he forged. In remembering John Opitz, we honor not only a man, but also a myth-a symbol of resilience, humanity, and scientific excellence.CONCLUSIONJohn M. Opitz's towering intellect, compassionate demeanor, and profound impact on medicine and genetics made him a figure of enduring significance. His legacy lives on through the countless lives he touched, the knowledge he transmitted, and the enduring friendships he forged. In remembering John Opitz, we honor not only a man, but also a myth-a symbol of resilience, humanity, and scientific excellence.
Summary
To facilitate an integrated and rational approach to the care of women with epilepsy of childbearing potential, a group of experts appointed by Italian scientific societies in the fields of ...epileptology, neonatology, pediatrics, neuropediatrics, child neuropsychiatry, obstetrics, and gynecology held a joint meeting in Santa Trada di Cannitello, Reggio Calabria, Italy, on October 15–16, 2004, with the aim of reaching consensus on the optimal management of these women. An ad hoc system for the classification of available published evidence and the opinions of experts was developed and used to grade recommendations on different aspects related to counseling, diagnostic, and treatment issues. The present document summarizes available evidence on the reciprocal interactions between epilepsy, antiepileptic drugs, fertility, contraception, pregnancy, delivery, breastfeeding, and the offspring. Recommendations are made concerning the information and counseling that should be provided to women with epilepsy with respect to issues related to contraception, conception, pregnancy, labour, and puerperium. More detailed recommendations on the same issues are provided to physicians and other healthcare professionals involved in the care of these women, with special reference to choice of effective contraception, optimization of antiepileptic drug therapy, use of prenatal diagnostic tests and other monitoring procedures, and appropriate management practices in relation to childbirth, puerperium, and the care of the child.
Aim The aim of this article was to review and conduct a meta‐analysis of the paediatric literature on the neurology of coeliac disease.
Method We conducted a review of paediatric studies published ...in English assessing neurological illness in coeliac disease identified through a MEDLINE search (1950–2009). Calculation of computed relative risk, odds ratio, and risk difference was performed using the fixed effect method if applicable.
Results Fifteen studies were analysed (11 772 participants). The meta‐analysis showed that (1) the relative risk of epilepsy in individuals with coeliac disease, and of coeliac disease in individuals with epilepsy, compared with the general population, was 2.1 and 1.7, respectively, and the risk difference was close to zero, indicating that it was probably a chance association; and (2) the relative risk of headache in individuals with the disease compared with comparison groups was 3.2. In two studies, cerebellar ataxia was documented in 2.7 to 5.4% of participants; in two further studies, the risk of cerebellar dysfunction was zero. Two studies found an association between coeliac disease and peripheral neuropathy. Brain white matter lesions were recorded in two other studies. An association between autism and coeliac disease is disputed.
Interpretation Children with coeliac disease are at risk of developing neurological complications, but the risk is lower than in adulthood. The discrepancy might be due to short disease duration, early elimination of gluten from the diet, stricter adherence to diet, or different susceptibility to immune‐mediated disorders.
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