Catia Romano

Pediatric Autoimmune Encephalitis.

Autoimmune (antibody mediated) encephalitis (AE) is emerging as a more common cause of pediatric encephalopathy than previously thought. The autoimmune process may be triggered by an infection, vaccine, or occult neoplasm. In the latter case, onconeural autoantibodies are directed against intracellular neuronal antigens, but a recent heterogeneous group of encephalitic syndromes has been found not to have underlying tumor but is associated with autoantibodies to the neuronal surface or synaptic antigens. Neuropsychiatric symptoms are very common in autoimmune encephalopathy; as a result, affected children may be initially present to psychiatrists. Neurological features are movement disorders, seizures, altered conscious level, and cognitive regression. Hypoventilation and autonomic features may be an aspect. Inflammatory findings in the cerebrospinal fluid may be present but are relatively nonspecific. Magnetic resonance imaging (MRI) may also demonstrate abnormalities that provide clues for diagnosis, particularly on fluid-attenuated inversion recovery or T2-weighted images. AE is well responsive to immune therapy, with prompt diagnosis and treatment strongly beneficial. Patients with paraneoplastic encephalitis are more refractory to treatment compared to those in whom no malignancy is identified. Herein, the authors present an update of literature data on the clinical presentation, laboratory and imaging findings, therapy, and outcomes for the most common autoimmune encephalitides.

The Gut–brain axis: A new pathogenic view of neurologic symptoms – Description of a pediatric case

Recent literature data have given emphasis to the relationship between gastrointestinal (GI) disorders and neurologic diseases, underlying a new pathogenic pathway: The so-called “gut–brain axis.” Herein, authors report a case of a 10-month-old male infant, admitted for drug-resistant epilepsy, associated with irritable behavior and GI discomfort, secondary to cows milk protein allergy. Seizures were described by parents as upward eye movements that were mostly deviated to the right and were associated with slight extension of his neck. They were infrequent at first, but had increased gradually during the course of 3 days (up to 15–20 times/day). No anticonvulsant therapy was effective. Only a cows milk protein-free diet, accidentally started during a gastroenteritis episode, was effective in stopping seizures. Our case underlines the peculiar vulnerability of the blood–brain barrier under 1 year of age, for which children of this age group experience neurologic manifestations during episodes of systemic inflammation.

Biological Drugs in Guillain-Barré Syndrome: An Update

Background: Guillain-Barré Syndrome (GBS) is currently considered the most common global cause of acute flaccid paralysis. Currently, standard therapy for Guillain-Barré Syndrome includes intravenous immunoglobulin or plasma exchange. Despite medical advances regarding these treatments, many treated patients do not reach full recovery. Therefore several biological agents have attracted the attentions from researchers during the last decades, and various studies have investigated their role in Guillain-Barré Syndrome. Objective: The present study aims to address emerging biological approaches to GBS while considering their efficiency and safety in treating the disease. Materials and Methods: An extensive electronic literature search was conducted by two researchers from April 2016 to July 2016. Original articles, clinical trials, systematic reviews (with or without meta-analysis) and case reports were selected. Titles and abstracts of papers were screened by reviewers to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved. Results: Herein authors focused on the literature data concerning emerging biological therapeutic agents, namely anti-C5 monoclonal antibody (Eculizumab), anti-C1q monoclonal antibody, anti-T cell monoclonal antibody, anti-CD2 monoclonal antibody, anti L-selectin monoclonal antibody, anti-CD20 monoclonal antibody (Rituximab), anti-CD52 monoclonal antibody (Alemtuzumab) and cytokine targets. By far, none of these agents have been approved for the treatment of GBS by FDA. Conclusion: Literature findings represented in current review herald promising results for using these biological targets. Current review represents a summary of what is already in regards and what progress is required to improve the immunotherapeutic approach of treating GBS via future studies.

Electrocardiographic Evaluation in Patients With Spinal Muscular Atrophy: A Case-Control Study

Background: This study aimed to show the impairment of autonomic cardiac conduction causing bradycardia and/or electrocardiographic alterations in children affected by spinal muscular atrophy type 1 and 2 (SMA 1 and 2). Methods: We included 25 spinal muscular atrophy patients, admitted from November 2016 to May 2017. All patients underwent an electrocardiographic examination and we studied PR and QRS intervals, P-waves and QRS amplitudes, and heart rate in spinal muscular atrophy patients compared to a control group. Results: In all patients, we found longer PRi and QRSi (P < .05), lower P-wave and QRS complex amplitudes (P < .01), and a decreased heart rate (P < .01) with respect to controls. When we divided our patients into SMA1 and SMA2 subgroups, we found that statistical differences were maintained for P-wave and QRS complex amplitudes and heart rate, but not for PRi and QRSi with respect to controls. Conclusion: We suggest the hypothesis of SMN expression on cardiac tissue condition and/or autonomic cardiac conduction.

Pyridoxine Add-On Treatment for the Control of Behavioral Adverse Effects Induced by Levetiracetam in Children: A Case-Control Prospective Study

Background: Few studies on adult and pediatric patients have shown pyridoxine efficacy as additional therapy for those receiving levetiracetam (LEV) to prevent and mitigate behavioral adverse effects (BAEs). Objective: The aim of our study was to analyze the safety and efficacy of pyridoxine supplementation in the prevention of LEV adverse effects, including suicidal ideation. Methods: This randomized, case-control trial included patients receiving LEV as monotherapy treatment. Patients were subdivided into 2 groups, according to whether they were treated with LEV only (group 1) or LEV with supplemental pyridoxine (group 2). Results: In both cohorts, the most frequent BAEs were irritability/aggression followed by depression and confusion. Those patients (92%) who initiated pyridoxine after 1 month of LEV treatment did not need to change or suspend LEV (P < 0.001), and BAE improved after 9.06 ± 3.05 days of pyridoxine supplementation. None of the patients complained of symptoms of pyridoxine toxicity, and no new adverse effects of LEV off-label were reported. Conclusions: In our study, we found pyridoxine to be safe and effective in controlling LEV-induced BAEs in children.

Spinal motor neuron involvement in a patient with homozygous PRUNE mutation

In the last few years, whole exome sequencing (WES) allowed the identification of PRUNE mutations in patients featuring a complex neurological phenotype characterized by severe neurodevelopmental delay, microcephaly, epilepsy, optic atrophy, and brain or cerebellar atrophy. We describe an additional patient with homozygous PRUNE mutation who presented with spinal muscular atrophy phenotype, in addition to the already known brain developmental disorder. This novel feature expands the clinical consequences of PRUNE mutations and allow to converge PRUNE syndrome with previous descriptions of neurodevelopmental/neurodegenerative disorders linked to altered microtubule dynamics.