“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

Migraine treatment in developmental age: guidelines update

There is a serious lack of controlled studies on the pharmacological treatment of primary migraine in the developmental age; there is, consequently, an urgent need for new, evidence-based approaches to this long-neglected field of research. Moreover, previous studies have stated that the placebo response is greater in pediatric patients than in adults and that a reduction in the attack frequency in the absence of any pharmacological treatment is observed more frequently in pediatric migraine patients than in adults. Besides these preliminary considerations, the shorter duration of migraine attacks and other characteristic semeiological features of the clinical picture in children are such that the design of randomized controlled trial (RCT) is more problematic in the developmental age than in the adult. Bearing in mind all these weak points, the aim of this review was to summarize and update recent guidelines for the treatment of primary migraine in children and adolescents. The most recent guidelines are those published by the Italian Society for the study of Headache, the French Society for the study of Migraine and Headache, and the American Academy of Neurology. We have incorporated into these guidelines the results from the few, recent RCTs, clinical controlled trials, open-label studies, meta-analyses and reviews that have been published since 2004; owing to the lack of strong evidence in this field of research, we have sometimes even mentioned pilot noncontrolled studies, case series and expert opinions. Lastly, evidence was classified and the recommendations were categorized according to different levels

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

Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala

Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience

Recent development in neuronal migration disorders: clinical, neuroradiologic and genetics aspects

Disorders of neuronal migration are a heterogeneous group of disorders of nervous system development. One of the most frequent disorders is lissencephaly characterized by a paucity of normal gyri and sulci resulting in a "smooth brain". There are two pathologic subtypes: classical and cobblestone. Classical lissencephaly results from an arrest of neuronal migration, whereas cobblestone lissencephaly results from overmigration. Another important neuronal migration disorder is heterotopia characterized by a cluster of normal neurons in abnormal locations and it is divided into three main groups: periventricular nodular heterotopia, subcortical heterotopia and marginal glioneural heterotopia. Polymicrogyria develops at the last stages of neuronal migration to the earliest phases of cortical organization; bilateral frontoparietal form is characterized by bilateral, symmetric polymicrogyria in the frontoparietal regions. Bilateral perisylvian polymicrogyria results in a clinical syndrome manifested by mild mental retardation, epilepsy and pseudobulbar palsy. Schizencephaly is another important disorder of neuronal migration whose clinical characteristics are extremely variable. Focal cortical dysplasia represents one of most severe causes of epilepsy in children. This review reports the main clinical, genetical, neuroradiological aspects of these disorders

NEUROCARDIOGENIC SYNCOPE AND EPILEPSY IN PEDIATRIC AGE: THE DIAGNOSTIC VALUE OF EEG-ECG HOLTER

Neurocardiogenic syncope is induced by a hyperrecruitment of parasympathetic nerve tone elicited by emotional stress or pain. The presence of a transient loss of consciousness associated with involuntary motor activity or with urinary incontinence and the misinterpretation of anamnestic data or of electroencephalogram (EEG) abnormalities often leads to wrong diagnosis of epilepsy in children with this disorder.Careful and systematic history taking, pressure measurement, electrocardiogram (ECG), and, in selected cases, head-up tilt table testing are generally enough to rule out a cardiogenic or a neurocardiogenic syncope. Simultaneous EEG-ECG Holter represents a useful instrument for differential diagnosis between neurocardiogenic syncope and epilepsy.We report 3 case reports to demonstrate how simultaneous EEG-ECG Holter can contribute to characterize functional heart-brain interactions and the exact sequence of the physiopathologic events leading to the loss of consciousness in cases in which the clinical borders with epileptic disorders are particularly subtle

Neurocardiogenic syncope and epilepsy in pediatric age: The diagnostic value of electroencephalogram-electrocardiogram holter

Neurocardiogenic syncope is induced by a hyperrecruitment of parasympathetic nerve tone elicited by emotional stress or pain. The presence of a transient loss of consciousness associated with involuntary motor activity or with urinary incontinence and the misinterpretation of anamnestic data or of electroencephalogram (EEG) abnormalities often leads to wrong diagnosis of epilepsy in children with this disorder.Careful and systematic history taking, pressure measurement, electrocardiogram (ECG), and, in selected cases, head-up tilt table testing are generally enough to rule out a cardiogenic or a neurocardiogenic syncope. Simultaneous EEG-ECG Holter represents a useful instrument for differential diagnosis between neurocardiogenic syncope and epilepsy.We report 3 case reports to demonstrate how simultaneous EEG-ECG Holter can contribute to characterize functional heart-brain interactions and the exact sequence of the physiopathologic events leading to the loss of consciousness in cases in which the clinical borders with epileptic disorders are particularly subtle. Copyright © 2011 by Lippincott Williams & Wilkins

Efficacy of verapamil as an adjunctive treatment in children with drug-resistant epilepsy. A pilot study

Purpose: Verapamil, a voltage-gated calcium channel blocker, has been occasionally reported to have some effect on reducing seizure frequency in drug-resistant epilepsy or status epilepticus. We aimed to investigate the efficacy of verapamil as add-on treatment in children with drug-resistant epilepsy. Methods: Seven children with drug-resistant structural-metabolic, unknown or genetic (e.g., Dravet syndrome [DS]) epilepsy received verapamil as an add-on drug to baseline antiepileptic therapy. Verapamil was slowly introduced at the dosage of 1 mg/kg/day and titrated up to 1.5 mg/kg/day. After completing the titration period, patients entered a 14-month maintenance period and were followed up at 3, 8, and 14 months. Heart monitoring was performed at baseline and at each follow-up. The primary outcome measure was the response of seizures to verapamil. Results: Three subjects with genetically determined DS showed a partial (reduction of 50-99%) response for all types of seizures. A patient with DS without known mutation showed a partial control of all types of seizures in the first 13 months; then seizures worsened and verapamil was suspended. Two patients with structural epilepsy and one with Lennox-Gastaut syndrome showed no improvement. Any side effects were recorded. Conclusions: Add-on treatment with verapamil seems to have some effect in controlling seizures in patients with genetically determined DS. Our observations justify further research on the relationship between calcium channels, calcium channel blockers, and channelopathies

Fiber tractography assessment in double cortex syndrome

Subcortical band heterotopia (SBH) or double cortex syndrome is a malformation of cortical development that may be related to intractable epilepsy and severe mental retardation or to mild epilepsy and slight mental delay or normal cognitive functions. Several studies have been performed using neuroradiological or neurophysiological techniques, like SPECT, PET, MRS, fMRI, and MEG, in attempt to better characterize this neuronal migration disorder. Recently, also diffusion tensor imaging (DTI) and fiber tracking (FT) have been used to investigate on white matter anomalies in SBH, adding more information about such gray matter anomaly. We report on three cases of SBH, evaluated with MRI, DTI, and FT. The data gathered from DTI and TF allow us to hypothesize a new functional role for heterotopic gray matter