Acute Disseminated Encephalomyelitis followed by Optic Neuritis: A Rare Syndrome of Uncertain Treatment and Prognosis.

AIM: Acute Disseminated Encephalomyelitis followed by optic neuritis (ADEM-ON), first described in 2013, is a rare demyelinating syndrome, typical of the pediatric age. We conducted a mini review of the existing literature, focusing on clinical, laboratory, radiological, therapeutic, and prognostic aspects in order to improve the identification of new cases. METHODS: We searched PubMed and Cochrane Library for studies on ADEM-ON between 2013 and 2018. RESULTS EXAMINATION: of the reported cases (three case reports and eight observational studies) established the following features. Time between ADEM and ON is highly variable. Almost all patients show antimyelin oligodendrocyte glycoprotein antibody (MOG-abs) seropositivity. High-dose intravenous steroid and plasmapheresis efficacy is reported for the acute phase; oral prednisone and other maintenance drugs may be useful in avoiding relapses. The clinical history may lead to a complete recovery but also to residual deficits. CONCLUSION: MOG-abs detection strongly supports ADEM-ON diagnosis, confirming this entity as part of MOG-abs spectrum disorder. Owing to the very small number of cases so far reported, predicting clinical evolution is very difficult.

Neuropsychiatric impairment in children with continuous spikes and waves during slow sleep: a long-term follow-up study.

A long-term follow-up study was conducted in patients affected by Continuous Spikes and Waves during slow Sleep (CSWS) to evaluate the long-term outcomes. Twenty-five patients (19 males, 6 females), from 2 to 16 years of age (mean age 6 years±3 SD), affected by CSWS syndrome, as defined by the International League Against Epilepsy (ILAE, 1989), were enrolled and followed for 11 years (mean duration of follow-up: 3.9 years). At the time of the appearance of CSWS, one or more neuropsychiatric disorders were present in 96% of the patients, such as behavioral problems in 54%, mental retardation in 37.5%, learning disabilities in 33%, developmental coordination disorder in 17%, language disorder in 12.5%, and pervasive developmental disorder in 8%. During the follow-up, neuropsychiatric dysfunctions remained unaltered in 52% of the patients, worsened in 24%, and improved in only 24%. Our data confirm that CSWS may be associated with a broad spectrum of neuropsychiatric disorders and may promote their worsening over time. Moreover, the findings cannot be generalized to all cases of children with CSWS because most of the children in the subgroups with no change in outcome and worse outcome had symptomatic CSWS.

Depressive risk among Italian socioeconomically disadvantaged children and adolescents during COVID-19 pandemic: a cross-sectional online survey.

BACKGROUND: Children and adolescents and low-income individuals are considered particularly vulnerable for mental health implications during the current COVID-19 pandemic. Depression is a frequent negative emotional response during an epidemic outbreak and is also prone importantly to environmental risk like stressors derived from income inequality. We aimed to assess depressive symptomatology in a sample of Italian low-income minors during the COVID-19 outbreak. We hypothesized that the stronger were the negative effects of the pandemic on socioeconomic conditions, the higher would have been the risk for showing depressive symptoms. METHODS: We performed a cross-sectional study during July 2020, at the end of the Italian first wave of COVID-19 pandemic. We recruited 109 Italian socioeconomically disadvantaged children and adolescents from 7 to 17 years. We used an online survey to collect socio-demographic and clinical data and information about pandemic-related stressors and to assess depressive symptoms with the Children's Depression Inventory 2 (CDI 2), Parent Version (Emotional Problems subscale) and Self-Report Short Form. We performed logistic regression analysis to assess the association between depressive symptoms and potential risk factors for mental health. RESULTS: 22% and 14% of participants showed depressive symptoms at the CDI 2 Parent Version and Self-Report, respectively. Participants coming from families experiencing a lack of basic supplies during the pandemic (34.9%) were more expected to show depressive symptoms at CDI 2 Parent Version. Participants with a pre-existing neuropsychiatric diagnosis (26.6%) were more likely to exhibit depressive symptoms measured by CDI 2 Parent Version. CONCLUSIONS: The results of our study showed that a group of Italian socioeconomically disadvantaged children and adolescents were more vulnerable to depressive symptoms if they suffered from a paucity of essential supplies during the pandemic or had pre-existing neurodevelopmental disorders. The promotion of educational and child-care programs and activities could be crucial in sustaining the prevention of mental distress in those frail subjects who particularly need support outside the family. Further studies are needed to detect effective preventive and therapeutic strategies to adopt promptly in the case of another pandemic wave.

Associations of High-Sensitivity C-Reactive Protein and Interleukin-6 with Depression in a Sample of Italian Adolescents During COVID-19 Pandemic.

Introduction: Many studies highlighted the role of inflammation in the pathogenesis of depression, although not for every patient nor for every symptom. It is widely shared that stressors can increase inflammation and lead to depressive symptoms. Little is known about the symptom-specificity of the inflammation-depression link in adolescence, which we aimed to explore. The single symptom analysis is a core feature of the recent network approach to depression, supposing that psychiatric disorders consist of co-occurring symptoms and their tendency to cause each other. Patients and Methods: We recruited 52 adolescents diagnosed with a Depressive Disorder during the COVID-19 stressful period. We used regression analysis to measure associations between high sensitivity C-Reactive Protein (hs-CRP) and Interleukin-6 (IL-6) and depressive symptoms assessed by the Children's Depression Inventory 2 (CDI 2). For the study of symptom specificity, we selected 13 items from the CDI 2 Self Report corresponding with the DSM-5 diagnostic criteria for Major Depressive Disorder and we coded them as dichotomous variables to perform a regression analysis. Results: We found that a higher CDI 2-Parent Version total score was significantly predicted by higher hs-CRP (coefficient 3.393; p 0.0128) and IL-6 (coefficient 3.128; p 0.0398). The endorsement of the symptom self-hatred, measuring the DSM-5 symptom "feelings of worthlessness", was significantly predicted by hs-CRP (OR 10.97; 95% CI 1.29-93.08; p 0.0282). Conclusion: A novel symptom-specificity emerged, with hs-CRP significantly predicting the endorsement of the symptom self-hatred, recognized as a core feature of adolescent depression, following the network theory. We considered it a possible phenotypic expression of one depression endophenotype previously causally linked to inflammation. Due to the limited sample size, these preliminary findings require confirmation with future research focusing on the relationship between inflammation and self-hatred and other central nodes of the depression network, representing an opportunity for targeting interventions on crucial symptoms.

Assessing Clinical Features of Adolescents Suffering from Depression Who Engage in Non-Suicidal Self-Injury.

Depressive disorders (DDs) and non-suicidal self-injury (NSSI) are important juvenile mental health issues, showing alarming increasing rates. They frequently co-occur, mainly among adolescents, increasing the suicide risk. We aimed to compare the clinical features of two groups of adolescents with DDs, differed by their engagement or not in NSSI ("DD + NSSI" and "DD"). We hypothesized that NSSI would characterize particularly severe forms of DDs suitable for becoming specific phenotypes of adolescent depression. We enrolled 56 adolescents (11-17 years) diagnosed with a DD according to the DSM-5 criteria. They were assessed for NSSI endorsement (Ottawa Self-Injury Inventory), depressive symptoms (Children's Depression Inventory 2), emotional dysregulation (Difficulties in Emotional Regulation Scale), and anxiety symptoms (Screen for Child Anxiety-Related Emotional Disorders). The two groups accounted for 31 ("DD + NSSI") and 25 ("DD") individuals. The "DD + NSSI" group had significantly higher suicidal ideation (p 0.0039), emotional dysregulation (p 0.0092), depressive symptoms (p 0.0138), and anxiety symptoms (p 0.0153) than the "DD" group. NSSI seemed to characterize more severe phenotypes of adolescent depression, applying for a potential role as a "specifier" of DDs, describing relevant information for their management. Further studies are needed to support this hypothesis and its potential opportunities for prevention and treatment.

GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak.

Paroxysmal dyskinesias are episodic movement disorders that can be inherited or are sporadic in nature. The pathophysiology underlying these disorders remains largely unknown but may involve disrupted ion homeostasis due to defects in cell-surface channels or nutrient transporters. In this study, we describe a family with paroxysmal exertion-induced dyskinesia (PED) over 3 generations. Their PED was accompanied by epilepsy, mild developmental delay, reduced CSF glucose levels, hemolytic anemia with echinocytosis, and altered erythrocyte ion concentrations. Using a candidate gene approach, we identified a causative deletion of 4 highly conserved amino acids (Q282_S285del) in the pore region of the glucose transporter 1 (GLUT1). Functional studies in Xenopus oocytes and human erythrocytes revealed that this mutation decreased glucose transport and caused a cation leak that alters intracellular concentrations of sodium, potassium, and calcium. We screened 4 additional families, in which PED is combined with epilepsy, developmental delay, or migraine, but not with hemolysis or echinocytosis, and identified 2 additional GLUT1 mutations (A275T, G314S) that decreased glucose transport but did not affect cation permeability. Combining these data with brain imaging studies, we propose that the dyskinesias result from an exertion-induced energy deficit that may cause episodic dysfunction of the basal ganglia, and that the hemolysis with echinocytosis may result from alterations in intracellular electrolytes caused by a cation leak through mutant GLUT1.

Pediatric Optic Neuritis: Description of Four Cases and Review of the Literature.

Pediatric optic neuritis (PON) may be a clinically isolated and self-limiting event or may present in the context of underlying neurologic, infective, or systemic disease. PON has a high impact on the quality of life as it may or may not evolve into other acquired demyelinating syndromes (ADSs), such as multiple sclerosis (MS), neuromyelitis optica (NMO), or other syndromes related to the myelin oligodendrocyte glycoprotein IgG antibodies (MOG-IgG). These different PON phenotypes present variable clinical and radiological features, plasma and liquor biomarkers, and prognosis. We describe four pediatric cases presenting clinically with ON, with different etiopathogenetic pictures: one case had a probable infective etiology, while the others were associated with different demyelinating disorders (MS, NMO, syndrome related to MOG-IgG). We discuss the possible evolution of presenting ON in other ADSs, based on recent literature. A careful evaluation of the clinical and investigation findings and the natural course of PON is necessary to define its pathogenic pathway and evolution. Further prolonged follow-up studies are needed to highlight the predictors of PON evolution, its potential sequelae, and the best treatment options.

Costello syndrome: cognitive and proton magnetic resonance spectroscopy findings--a case report.

The authors describe a girl with Costello syndrome who showed cerebral palsy and neurosensorial deafness. Brain computer tomography and magnetic resonance findings were normal. Multivoxel proton magnetic resonance spectroscopy showed a lowering of the peak of choline with a reduced choline/creatine ratio at the level of the centrum semiovale. These findings might be due to a congenital dysmyelinating or hypomyelinating condition. A complete neuroimaging study can play a relevant role to better clarify the pathogenesis of brain involvement in Costello syndrome.

Mental retardation and epilepsy in patients with isolated cerebellar hypoplasia.

Congenital nonprogressive cerebellar ataxia includes a complex group of disorders with heterogeneous phenotypic and etiopathogenetic characteristics. Despite recent advances in the understanding of the role of the cerebellum in cognition and behavior, the opinion that the clinical presentation of congenital cerebellar diseases is principally linked to motor dysfunction is common. This is largely due to the lack of well-organized epidemiologic studies on the prevalence of nonmotor disturbances in cerebellar disease. The association between congenital cerebellar disease and epilepsy has rarely been described. We report clinical, neurophysiologic, neuroimaging, and neuropsychologic features in a group of 14 patients with congenital nonprogressive cerebellar ataxia associated with cerebellar hypoplasia, 5 of whom have familial disease, aiming to further a better knowledge of the prevalence of cognitive and/or emotional impairment and epilepsy. The results confirm that cerebellar hypoplasia predisposes individuals to psychomotor delay (71.4%) and cognitive impairment (85.7%). Moreover, the tendency toward abnormal electroencephalographic (EEG) findings (78.5%), associated in a minor percentage of cases with epilepsy (28.5%), is also evident in our study.

Clinical and instrumental (magnetic resonance imaging [MRI] and multimodal evoked potentials) follow-up of brain lesions in three young patients with neurofibromatosis 1.

Diagnosis of neurofibromatosis 1 is based on clinical criteria. In a large number of children with neurofibromatosis 1, magnetic resonance imaging (MRI) reveals high-signal T(2)-weighted intensities in different brain regions, defined as unidentified bright objects. These lesions are asymptomatic; most of them regress spontaneously with age, but the presence of contrast enhancement or mass effect in them usually strongly suggests an increased risk of proliferative changes. To date, few studies have focused on evoked potentials in patients with neurofibromatosis 1, and the reported abnormalities did not have significant clinical correlations. We describe the clinical and instrumental (MRI and evoked potentials) follow-up of three patients with neurofibromatosis 1. MRI and evoked potentials showed subclinical involvement of the central nervous system. Some MRI T(2)-weighted hyperintensities showed enhancement and mass effect of uncertain significance. During follow-up, the MRI lesions spontaneously decreased in size or enhancement, allowing us to exclude the hypothesis of proliferative lesions; in the same way, some asymptomatic evoked potential abnormalities disappeared. These findings suggest that both MRI and evoked potentials could be useful in the detection and monitoring of cerebral complications of neurofibromatosis 1.

Megalocornea and mental retardation syndrome: clinical and instrumental follow-up of a case.

Megalocornea-mental retardation syndrome, otherwise known as Neuhauser syndrome, is a rare autosomal recessive disorder. Only 36 cases have been reported in the literature. We describe the clinical and instrumental follow-up, lasting 5 years, of a case showing the typical features of the syndrome, associated with transient hypothyroidism, epilepsy, cerebral palsy with choreoathetotic movements, and brain malformation. Our report might help better delineate the phenotype and natural history of the syndrome.

Brain magnetic resonance spectroscopy in Sydenham's chorea and ADHD.

This report presents clinical, laboratory, and neuroimaging findings in a 7-year-old male with Sydenham's chorea associated with attention-deficit hyperactivity disorder. Western immunoblotting revealed serum anti-human basal ganglia tissue antibodies. Magnetic resonance imaging results were normal. Proton magnetic resonance spectroscopic imaging disclosed increased choline/creatine ratio in basal ganglia, frontal, and parieto-occipital areas, and decreased N-acetyl aspartate/creatine ratio in both basal ganglia and frontal areas. Moreover magnetic resonance spectroscopy revealed a peak between 3.6-4.2 ppm of unclear significance. The findings of this study are compared with the previous magnetic resonance spectroscopic studies reported on Sydenham's chorea and attention-deficit hyperactivity disorder. Magnetic spectroscopic imaging suggests an autoimmune basal ganglia damage in the pathogenesis of Sydenham's chorea and fronto-striatal impairment in attention-deficit hyperactivity disorder. In the present case, the previous history of an attention-deficit hyperactivity disorder suggests that this neurobehavioral disorder could be a risk factor for Sydenham's chorea in children with rheumatic fever.

Congenital bilateral perisylvian syndrome with partial epilepsy. Case report with long-term follow-up.

Congenital bilateral perisylvian syndrome (CBPS) is a rare neurological disorder characterised by pseudobulbar palsy, cognitive deficits and epilepsy associated with bilateral perisylvian cortical dysplasia on neuroimaging studies. We report a long-term follow-up of a 18-years girl diagnosed with CBPS according to the typical clinical and magnetic resonance imaging (MRI) features. The patient showed faciopharyngoglossomasticatory diplegia, severe dysarthria, ataxia, spastic quadriparesis and severe mental retardation. Brain MRI evidenced bilateral perisylvian cortical dysplasia. Since early life she suffered from complex febrile seizures and epilepsy consisting of complex partial attacks with affective manifestations associated with centro-temporal EEG abnormalities. During 18 years of follow-up she was treated with phenobarbital, carbamazepine, lamotrigine, gabapentin but did not show any significant clinical improvement. Subsequently, monotherapy with phenytoin (PHT) was followed by a significant clinical improvement. At age 17, because of adverse effects, PHT was gradually substituted by topiramate (TPM). Full control of seizures was obtained at the age of 17 years with TPM. EEG abnormalities throughout the years have been reduced according to the clinical course. These findings emphasised the importance of long-term follow-up, suggesting that the prognosis for epilepsy may not be predicted based on the early response to treatment or on the presence of structural encephalic abnormalities, as reported in the literature.

Channelopathy: hypothesis of a common pathophysiologic mechanism in different forms of paroxysmal dyskinesia.

Paroxysmal dyskinesias are a rare heterogeneous group of neurologic disorders, characterized by transient sudden choreoathetoid or dystonic attacks without loss of consciousness. This study reports a family with six affected members in three generations, and two sporadic cases of paroxysmal dyskinesia. Familial cases of paroxysmal dyskinesia are affected by idiopathic long-lasting paroxysmal exertion-induced dyskinesia and the sporadic cases by idiopathic short-lasting paroxysmal kinesigenic dyskinesia. Familial cases also suffer from epilepsy, mainly of generalized type, with benign outcome; one sporadic case is affected by migraine. Results presented in this neurophysiologic study include electromyography, somatosensory evoked potentials by median nerve stimulation, somatosensory evoked potentials by posterior tibial nerve stimulation, motor evoked potentials by magnetic transcranial cortical stimulation, visual evoked potentials, brainstem auditory evoked potentials, blink reflex, reflex H, and electroencephalography. The clinical and neurophysiologic findings presented here suggest a condition of hyperexcitability at the muscular and brain level, perhaps as a result of an ion channel disorder, which is in agreement with reports in the literature.

Congenital ataxia and mental retardation in three brothers.

Nonprogressive congenital ataxia is a complex group of disorders caused by a variety of etiologic factors, both environmental and genetic. Hereditary forms represent a substantial part of congenital ataxias, which are difficult to classify because of their phenotypic and genetic polymorphism. Despite the advances in molecular genetics, for most nonprogressive congenital ataxia the etiology is still unknown. This report describes three sons of nonconsanguineous healthy parents, who manifested a syndrome characterized by nonprogressive ataxia, mental retardation, pyramidal signs, ocular and ocular motor anomalies, associated with severe hypoplasia of the cerebellar vermis and hemispheres on neuroimaging. All the patients have presented psychomotor developmental delay. As differential diagnosis, a comparison is made between the clinical features of these patients and the previously reported cases of nonprogressive congenital ataxia. This report represents a further example of the phenotypic and genetic heterogeneity of the syndromes with congenital ataxia.

Cerebral venous thrombosis after lumbar puncture and intravenous high dose corticosteroids: a case report of a childhood multiple sclerosis.

The association between cerebral venous thrombosis (CVT) and multiple sclerosis (MS) has already been reported in several adult patients with clinically definite MS, in a suspected relation to i.v. corticosteroids or previously performed lumbar puncture (LP). We are reporting a case, which is, to our knowledge, the first one concerning a child patient with a MS, who developed multiple CVT after LP and during high-dose i.v. corticosteroid. Our conclusions are that the sequence LP followed by high dose corticosteroids may be a contributory factor for the development of CVT when associated with other risk factors.

Very early onset and greater vulnerability in schizophrenia: A clinical and neuroimaging study.

Although schizophrenia has been diagnosed in children, this group of disorders has received too little attention in the clinical and research literature. Preliminary data suggest that early onset schizophrenia (EOS) and very early onset schizophrenia (VEOS) tend to have a worse outcome than adult onset schizophrenia, and seem to be related to a greater familial vulnerability, due to genetic, psychosocial, and environmental factors. Recently, advanced neuroimaging techniques have revealed structural and functional brain abnormalities in some cerebral areas. This paper reports on a case diagnosed as VEOS, with premorbid year-long psychopathological history. The patient showed atypical proton magnetic resonance spectroscopy findings, and normal brain and spine computer tomography and brain magnetic resonance images.

Electrophysiological study in 2 children with transient hypohidrosis induced by topiramate.

OBJECTIVE: Hypohidrosis, often associated with hyperthermia, has been reported, mostly in children, as a rare and reversible adverse effect of topiramate, an anticonvulsant drug with a broad spectrum of antiepileptic activity. The aim of our study is to detect a possible skin innervation involvement as the mechanism underlying hypohidrosis in children treated with topiramate. METHODS: A neurophysiological study has been performed on 2 children who have developed hypohidrosis under topiramate treatment. Electrophysiological data have been recorded during topiramate treatment and compared with a control group. Sympathetic skin responses have been recorded during topiramate assumption and after its discontinuation. RESULTS: In our 2 cases with hypohidrosis related to topiramate, electrophysiological study showed normal function of both beta and delta sensory fibers and absent sympathetic skin responses that recovered to normal after topiramate discontinuation. CONCLUSIONS: Our findings confirm that topiramate might induce a transitory specific carbonic anhydrase block at the level of sweat glands, without involvement of peripheral nervous system.