The diagnostic and prognostic role of cerebrospinal fluid biomarkers in glucose transporter 1 deficiency: a systematic review.

The purpose of this study is to investigate the diagnostic and prognostic role of cerebrospinal fluid (CSF) biomarkers in the diagnostic work-up of glucose transporter 1 (GLUT1) deficiency. Reported here is a systematic review according to PRISMA guidelines collecting clinical and biochemical data about all published patients who underwent CSF analysis. Clinical phenotypes were compared between groups defined by the levels of CSF glucose (≤ 2.2 mmol/L versus > 2.2 mmol/L), CSF/blood glucose ratio (≤ 0.45 versus > 0.45), and CSF lactate (≤ 1 mmol/L versus > 1 mmol/L). Five hundred sixty-two patients fulfilled the inclusion criteria with a mean age at the diagnosis of 8.6 ± 6.7 years. Patients with CSF glucose ≤ 2.2 mmol/L and CSF/blood glucose ratio ≤ 0.45 presented with an earlier onset of symptoms (16.4 ± 22.0 versus 54.4 ± 45.9 months, p < 0.01; 15.7 ± 23.8 versus 40.9 ± 38.0 months, p < 0.01) and received an earlier molecular genetic confirmation (92.1 ± 72.8 versus 157.1 ± 106.2 months, p < 0.01). CSF glucose ≤ 2.2 mmol/L was consistently associated with response to ketogenic diet (p = 0.018) and antiseizure medications (p = 0.025). CSF/blood glucose ratio ≤ 0.45 was significantly associated with absence seizures (p = 0.048), paroxysmal exercise-induced dyskinesia (p = 0.046), and intellectual disability (p = 0.016) while CSF lactate > 1 mmol/L was associated with a response to antiseizure medications (p = 0.026) but not to ketogenic diet.Conclusions:This systematic review supported the diagnostic usefulness of lumbar puncture for the early identification of patients with GLUT1 deficiency responsive to treatments especially if they present with co-occurring epilepsy, movement, and neurodevelopmental disorders. What is Known: • Phenotypes of GLUT1 deficiency syndrome range between early epileptic and developmental encephalopathy to paroxysmal movement disorders and developmental impairment What is New: • CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with early onset absences • CSF blood/glucose ratio may predict better than CSF glucose the diagnosis in children presenting with paroxysmal exercise induced dyskinesia and intellectual disability. • CSF glucose may predict better than CSF blood/glucose and lactate the response to ketogenic diet and antiseizure medications.

Psychiatric Manifestations in Children and Adolescents with Inherited Metabolic Diseases.

Background: Inherited metabolic disorders (IEMs) can be represented in children and adolescents by psychiatric disorders. The early diagnosis of IEMs is crucial for clinical outcome and treatment. The aim of this review is to analyze the most recurrent and specific psychiatric features related to IEMs in pediatrics, based on the onset type and psychiatric phenotypes. Methods: Following the PRISMA Statement, a systematic literature review was performed using a predefined algorithm to find suitable publications in scientific databases of interest. After removing duplicates and screening titles and abstracts, suitable papers were analyzed and screened for inclusion and exclusion criteria. Finally, the data of interest were retrieved from the remaining articles. Results: The results of this study are reported by type of symptoms onset (acute and chronic) and by possible psychiatric features related to IEMs. Psychiatric phenomenology has been grouped into five main clinical manifestations: mood and anxiety disorders; schizophrenia-spectrum disorders; catatonia; eating disorders; and self-injurious behaviors. Conclusions: The inclusion of a variety of psychiatric manifestations in children and adolescents with different IEMs is a key strength of this study, which allowed us to explore the facets of seemingly different disorders in depth, avoiding possible misdiagnoses, with the related delay of early and appropriate treatments.

Non-Pharmacological Treatments in Paediatric Migraine.

Psychological, social, and biological aspects contribute synergistically to the maintenance and chronicity of pain in primary headaches. An integrated intervention seems to be the most appropriate in the management of these conditions, taking advantage not only of pharmacological strategies, but also of different approaches according to the global assessment and patient necessities. In this perspective, non-pharmacological treatments are becoming increasingly used to overcome these issues also in paediatric migraine treatment. Particularly, nutraceuticals, non-invasive neuromodulation, and behavioural approaches are well tolerated and of potential interest. This paper aims to present the main approaches reported in the literature in the management of migraine in children and adolescents presenting an up-to-date review of the current literature. We therefore performed a narrative presentation for each of these three categories: nutraceuticals (riboflavin; magnesium; melatonin; vitamin D; coenzyme Q10; and polyunsaturated fatty acid); non-invasive neuromodulation (trigeminal nerve stimulator; non-invasive vagal nerve stimulation; transcranial magnetic stimulation; and remote electrical neuromodulation), and behavioural therapies (biofeedback; cognitive behavioural therapy; and mindfulness-based therapy). These approaches are increasingly seen as a valid treatment option in primary headache management also in paediatrics, avoiding medication overuse and drug treatment contraindications.

Using pharmacotherapy to address sleep disturbances in autism spectrum disorders.

INTRODUCTION: Sleep disorders are the second most common medical comorbidity in autism spectrum disorder (ASD), with effects on daytime behavior and functioning, mood and anxiety, and autism core features. In children with ASD, insomnia also has a negative impact on the whole family's quality of life. Therefore, treatment of sleep disturbances should be considered as a primary goal in the management of ASD patients, and it is important to clarify the scientific evidence to inappropriate treatments. AREAS COVERED: The authors review the current literature concerning the pharmacological treatment options for the management of sleep-related disorders in patients with ASD (aged 0-18 years) using the PubMed and Cochrane Library databases with the search terms: autism, autistic, autism spectrum disorder, ASD, drug, drug therapy, drug intervention, drug treatment, pharmacotherapy, pharmacological treatment, pharmacological therapy, pharmacological intervention, sleep, sleep disturbance, and sleep disorder. EXPERT OPINION: Currently, clinicians tend to select medications for the treatment of sleep disorders in ASD based on the first-hand experience of psychiatrists and pediatricians as well as expert opinion. Nevertheless, at the present time, the only compound for which there is sufficient evidence is melatonin, although antihistamines, trazodone, clonidine, ramelteon, gabapentin, or suvorexant can also be considered for selection.