“Epileptic Encephalopathy” of Infancy and Childhood: Electro-Clinical Pictures and Recent Understandings

There is growing interest in the diagnosis of cognitive impairment among children with epilepsy. It is well known that status of seizures control has to be carefully investigated because it can be sufficient “per se” to cause progressive mental deterioration conditions. Subclinical electroencephalographic discharges may have subtle effects on cognition, learning and sleep patterns, even in the absence of clinical or sub-clinical seizures. In this respect, electroencephalographic monitoring (long-term and nocturnal recording) and in particular an all night video-polysomnography (V-NPSG) record can be crucial to detect the presence of unrecognized seizures and/or an inter-ictal nocturnal EEG discharge increasing. Epileptic encephalopathies (EE) are a group of conditions in which the higher cognitive functions are deteriorate as a consequence of epileptic activity, which, in fact, consists of frequent seizures and/or florid and prolonged interictal paroxysmal discharges, focal or generalized. AEDs represent the first line in opposing the burden of both, the poor seizures control and the poor interictal discharges control, in the cognitive deterioration of EE affected children. Thus, to improve the long-term cognitive/behavioural prognosis in these refractory epileptic children, it should be taken into account both a good seizures control and a strict sleep control, choosing carefully antiepileptic drugs which are able to control not only seizures clinically recognizable but even the EEG discharges onset and its increasing and spreading during sleep. Here, we review the efficacy and safety of the newer AEDs that, to date, are used in the treatment of EE in infancy and childhood

Opsoclonus-Myoclonus Syndrome in Children and Adolescents:A Therapeutic Challenge

Opsoclonus-myoclonus syndrome (OMS) is a neurological non-fatal disease that usually responds to immunotherapies. However, the real challenge is to counteract the high frequency of relapses and long-term developmental sequelae. Since the OMS is extremely rare, a common consensus regarding therapeutic guidelines is still lacking. The goals of this study were to test whether ACTH was superior to other immunotherapies and to investigate whether an early treatment could improve the outcome. Sixteen children affected by OMS were retrospectively reviewed. Eight children had a neuroblastic tumor. The other eight patients were affected by non-paraneoplastic OMS. Overall, the most commonly used treatment was corticotherapy (n = 11). However, ACTH (n = 10), rituximab (n = 7), immunoglobulins (n = 4), cyclophosphamide (n = 3), and mycophenolate (n = 2) were also administered. ACTH was associated with a high percentage of patients who healed (80%) and, as a first-line therapy, was associated with a lower incidence of relapses. An early treatment was associated with a favorable long-term outcome. Long-term sequelae occurred in 42% of patients who were treated early and in all of those who were treated late. It is advisable for the affected children to be identified at an early time, as they may benefit from an early treatment. ACTH represents an effective treatment with a high probability of recovery and low rate of relapses

Prophylactic Treatment of Pediatric Migraine:Is There Anything New in the Last Decade?

Migraine is a frequent and very disabling disease, especially at pediatric age. Despite this, there are few controlled data on the prophylactic treatment of primary headaches in this category of age. Given that the recently introduced calcitonin gene-related peptide (CGRP) inhibitors (CGRP-r) are still limited to adulthood, there is no drug with exclusive indication for migraine treatment in pediatric age. This raises several limitations in terms of adherence and effectiveness of the therapy. Moreover, the scenario is complicated by placebo response, which is larger in children and adolescents than in adults and often leads to an improvement in the attack frequency even in absence of any active pharmacological treatment. Our aim was to investigate the real evidence concerning the prophylactic therapy of pediatric migraine by reviewing the clinical studies published between 2010 and 2019

Visual Disturbances Spectrum in Pediatric Migraine

Migraine is a complex neurological disorder with partially unknown pathophysiological mechanisms. The prevalence in childhood ranges from 7.7% to 17.8%, thus representing the most frequent primary headache. In half of the cases, migraine is accompanied or preceded by various neurological disturbances, among which the visual aura is the best known. In literature, other conditions, such as Alice in Wonderland Syndrome and Visual Snow syndrome, are characterized by visual manifestations and are often associated with migraine. The aim of this narrative review is to describe the spectrum of visual disturbances in pediatric migraine and their pathophysiological mechanisms

Clinical and Pharmacological Aspects of Inflammatory Demyelinating Diseases in Childhood: An Update

Inflammatory demyelinating diseases comprise a spectrum of disorders affecting the myelin of the central and peripheral nervous system. These diseases can usually be differentiated on the basis of clinical, radiological, laboratory and pathological findings

Real Life Data on OnabotulinumtoxinA for Treatment of Chronic Migraine in Pediatric Age

Background: the use of OnabotulinumtoxinA (OBT-A) for the treatment of chronic migraine (CM) in adults represents a therapy with the greatest efficacy and safety data. However, we have little evidence on the use of OBT-A in children or adolescents. The present study aims to describe the experience with OBT-A in the treatment of CM in adolescents in an Italian third-level headache center. Methods: the analysis included all patients under the age of 18 treated with OBT-A for CM at the Bambino Gesu Children's Hospital. All patients received OBT-A following the PREEMPT protocol. Subjects were classified as good responders if a greater than 50% reduction in the monthly frequency of attacks was observed, partial responders if the reduction was between 30 and 50%, and non-responders if it was <30%. Results: the treated population consisted of 37 females and 9 males with a mean age of 14.7 years. Before starting OBT-A, 58.7% of the subjects had attempted prophylactic therapy with other drugs. From OBT-A initiation to the last clinical observation, the mean duration of follow-up was 17.6 +/- 13.7 SD (range: 1-48) months. The number of OBT-A injections were 3.4 +/- 3 SD. Sixty eight percent of the subjects responded to treatment within the first three administrations of OBT-A. Proceeding with the number of administrations, a progressive improvement in frequency was further observed. Conclusions: the use of OBT-A in pediatric age can have benefits in terms of reduction in the frequency and intensity of headache episodes. Furthermore, treatment with OBT-A has an excellent safety profile. These data support the use of OBT-A in the treatment of childhood migraine

Medication Overuse Withdrawal in Children and Adolescents Does Not Always Improve Headache:A Cross-Sectional Study

Background:MOH can be diagnosed in subjects with headache occurring 15 days/month in association with a regular medication overuse, but its existence is not universally accepted. ICHD-3 redefined criteria for MOH, removing the criterion associating drug suspension with headache course. The aim of our study was to compare the rate of patients diagnosed with medication overuse headache (MOH) according to ICHD-2 and ICHD-3 criteria, to verify the degree of concordance. The secondary aim was to verify if drug withdrawal was really associated with pain relief. Methods:In this cross-sectional study, we retrospectively analyzed a sample of 400 patients followed for primary chronic headache at the Headache Center of Bambino Gesu Children's Hospital. We then selected those presenting with a history of medication overuse, and we applied both ICHD-2 and ICHD-3 criteria to verify in which patients the criteria would identify a clinical diagnosis of MOH. Results:We identified 42 subjects (10.5%) with MOH; 23 of them (55%) presented a relief of headache withdrawing drug overuse. Regarding the applicability of the ICHD-2 criteria, 43% of patients (18/42) fulfilled all criteria, while all ICHD-3 diagnostic criteria were satisfied in 76% of patients (32/42). Eighteen patients (43%) satisfied both ICHD-2 and ICHD-3 criteria, while 10 patients (24%) did not satisfy either diagnostic criterion. Conclusions:Our study suggests that in children and adolescents, withdrawing medication overuse is not always associated with a clinical benefit. Therefore, though allowing a MOH diagnosis in a higher rate of patients as compared to ICHD-2, the application of ICHD-3 criteria does not guarantee a true a causal relationship between medication overuse and headache worsening

Lifestyle Modifications to Help Prevent Headache at a Developmental Age

Headache is the world’s seventh most significant cause of disability-adjusted-life in people aged between 10 and 14 years. Therapeutic management is based on pharmacological approaches and lifestyle recommendations. Many studies show associations between each migraine-promoting lifestyle, behavioral triggers, frequency, and intensity of headaches. Nevertheless, the overall aspects of this topic lack any definitive evidence. Educational programs advise that pediatric patients who suffer from migraines follow a correct lifestyle and that this is of the utmost importance in childhood, as it will improve quality of life and assist adult patients in avoiding headache chronicity, increasing general well-being. These data are important due to the scarcity of scientific evidence on drug therapy for prophylaxis during the developmental age. The “lifestyle recommendations” described in the literature include a perfect balance between regular sleep and meal, adequate hydration, limited consumption of caffeine, tobacco, and alcohol, regular physical activity to avoid being overweight as well as any other elements causing stress. The ketogenic diet is a possible new therapeutic strategy for the control of headache in adults, however, the possible role of dietary factors requires more specific studies among children and adolescents. Educational programs advise that the improvement of lifestyle as a central element in the management of pediatric headache will be of particular importance in the future to improve the quality of life of these patients and reduce the severity of cephalalgic episodes and increase their well-being in adulthood. The present review highlights how changes in different aspects of daily life may determine significant improvements in the management of headaches in people of developmental age

Case report:A pediatric case of Bickerstaff brainstem encephalitis after COVID-19 vaccination and Mycoplasma pneumoniae infection: Looking for the culprit

Bickerstaff brainstem encephalitis (BBE) is a rare, immune-mediated disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance. It has a complex multifactorial etiology, and a preceding infectious illness is seen in the majority of cases. Immune-mediated neurological syndromes following COVID-19 vaccination have been increasingly described. Here we report the case of a child developing BBE 2 weeks after COVID-19 vaccination. Despite nerve conduction studies and CSF analysis showing normal results, BBE was diagnosed on clinical ground and immunotherapy was started early with a complete recovery. Later, diagnosis was confirmed by positive anti-GQ1b IgG in serum. Even if there was a close temporal relationship between disease onset and COVID-19 vaccination, our patient also had evidence of a recent Mycoplasma pneumoniae infection that is associated with BBE. Indeed, the similarity between bacterial glycolipids and human myelin glycolipids, including gangliosides, could lead to an aberrantly immune activation against self-antigens (i.e., molecular mimicry). We considered the recent Mycoplasma pneumoniae infection a more plausible explanation of the disease onset. Our case report suggests that suspect cases of side effects related to COVID-19 vaccines need a careful evaluation in order to rule out well-known associated factors before claiming for a causal relationship

Anxiety, Depression, and Body Weight in Children and Adolescents With Migraine

Background: There is a lack of studies that explore the possible association between body weight, psychological symptoms, and migraine severity in pediatric populations. The purpose of the study was to explore: (1) the association between body weight and the frequency of migraine attacks, (2) the possible differences in anxiety and depression symptoms according to the frequency of attacks and body weight, and (3) the possible mediating role of anxiety and/or depression in the association between body weight and frequency of migraine attacks in children.Methods: One hundred and eleven children/adolescents with migraine were included (47 boys and 64 girls; mean age 11.7; +/- 2.4 years). The patients were classified as: (1) high frequency patients, reporting from weekly to daily episodes and (2) low frequency patients, with <= 3 episodes per month. According to their body mass index percentiles, the patients were divided in "Normal weight" (from >= 5 to <85 percentile), "Overweight" (from >= 85 to <95 percentile), and "Obese" (>= 95 percentile). Given the low number of obese patients, the overweight and obese groups were considered together in the "Overweight" group. Anxiety and depression symptoms were assessed by the Self-Administered Psychiatric Scales for Children and Adolescents (SAFA).Results: Fifty-four patients were normal in weight (49.6%), while 56 patients (50.4%) were overweight. The overweight patients showed a higher frequency of migraine attacks (64.7%; p < 0.05). Patients with a high frequency of attacks reported higher scores in all SAFA-Anxiety subscales (SAFA-A Tot: F = 15.107; p = 0.000). Overweight patients showed a significantly higher score in the "Separation anxiety" subscale (F = 7.855; p = 0.006). We found a mediating role between the overweight and high frequency for total anxiety (z = 2.11 +/- 0.03; p < 0.05) and social anxiety (z = 2.04 +/- 0.03; p < 0.05).Conclusions: Our results suggest that, among the children suffering from migraine, the overweight status is associated with a higher frequency of attacks and separation anxiety symptoms. In particular, our study provides the first evidence of the role of anxiety in linking overweight and the frequency of migraine attacks in children and adolescents