Misdiagnosis of functional neurological symptom disorders in paediatrics: Narrative review and relevant case report.

Functional neurological symptom disorders (FNSD) pose a common challenge in clinical practice, particularly in pediatric cases where the clinical phenotypes can be intricate and easily confused with structural disturbances. The frequent coexistence of FNSDs with other medical disorders often results in misdiagnosis. In this review, we highlight the distinctions between FNSD and various psychiatric and neurological conditions. Contrary to the misconception that FNSD is a diagnosis of exclusion, we underscore its nature as a diagnosis of inclusion, contingent upon recognizing specific clinical features. However, our focus is on a critical learning point illustrated by the case of a 14-year-old male initially diagnosed with FNSD, but subsequently found to have a rare primary monogenic movement disorder (paroxysmal kinesigenic dyskinesia, PKD). The crucial takeaway from this case is the importance of avoiding an FNSD diagnosis based solely on psychiatric comorbidity and suppressible symptoms. Instead, clinicians should diligently assess for specific features indicative of FNSD, which were absent in this case. This emphasizes the importance of making a diagnosis of inclusion. Extended follow-up and clinical-oriented genetic testing might help identify comorbidities, prevent misdiagnosis, and guide interventions in complex cases, which cannot be simply classified as "functional" solely because other conditions can be excluded.

Understanding and Avoiding Mistakes in Diagnosing Children with Functional Neurological Symptom Disorders: A Review and Case Report: This article discusses Functional Neurological Symptom Disorders (FNSDs), focusing on misdiagnosis, differential diagnosis, and other diagnostic challenges, particularly in pediatric cases. FNSDs involve motor or sensory symptoms that are inconsistent over time and unexplained by neurological disease, often associated with psychosocial factors. The article highlights the complexity of distinguishing FNSDs from other neurological and psychiatric conditions, emphasizing the importance of careful evaluation. The authors review various conditions that can mimic FNSDs, such as epileptic seizures, syncope, and different motor disorders. They emphasize the need to consider psychiatric conditions in the differential diagnosis, including factitious disorders, and malingering. The article presents a case study of a 14-year-old with involuntary movements, initially diagnosed as having a Functional Movement Disorder. After careful evaluation, the patient was diagnosed with a genetic dystonia (PRRT2 mutation). The case shows the importance of not rely solely on psychological problems, bizarre presentations or suppressible symptoms when diagnosing FNSDs.

The Hidden Impact of ADHD Symptoms in Preschool Children with Autism: Is There a Link to Somatic and Sleep Disorders?

Neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), do often present in comorbidity among them and with other medical conditions, including sleep and gastrointestinal (GI) disorders and somatic complaints. An anonymous online survey based on standardized questionnaires (SDSC, KL-ASD, APSI, ROME V CRITERIA, CPRS, CBCL) was completed by the parents of 46 preschoolers diagnosed with ASD. A high prevalence (47%) of ADHD symptoms in this population was found, surpassing previous estimates. Sleep disturbances, especially difficulties in initiating and maintaining sleep and sleep-wake transition, are more pronounced in ASD patients with comorbid ADHD. Additionally, in patients over 4 years old, there is a high prevalence of functional GI symptoms (Rome V criteria: 38%). Parental stress is significantly associated with ADHD symptoms, sleep disorders, and GI symptoms. Comprehensive assessments considering both core symptoms of neurodevelopmental disorders and associated comorbidities are crucial for more effective treatment strategies and improved wellbeing in affected individuals and their families.

Sleep disturbances in subjects with autism spectrum disorder: A parental perspective.

OBJECTIVE: To investigate the prevalence of sleep disturbances (SDs), their related comorbidities, interventions and the impact on the family for individuals with current SDs and those who had SDs in the past. METHODS: Members of the Italian national association of parents of persons with autism (ANGSA) completed an anonymous online survey collecting demographic data, the presence of comorbidities and specific information on sleep arrangement and sleep disorders using a modified version of the of the Sleep Disturbance Scale for Children (SDSC). RESULTS: The final sample consisted of 143 participants, 90 patients presented current SDs (C_SDs) and 53 reported previous SDs (P_SDs). In the C_SDs group, the most prevalent sleep disorders were related to insomnia and, especially, difficulty falling asleep; a high number of individuals presented with restless sleep. Also, the parents in the P_SDs group retrospectively reported a high prevalence of insomnia with difficulty falling asleep, night awakenings and restless sleep. Parents reported that sleep hygiene practice were effective in less than one third of cases in both groups and the most used compound was immediate-release melatonin, followed by antihistamines and then benzodiazepines, antipsychotics, and antidepressants, with approximately 60-70% reported efficacy. Parents of both groups reported that insomnia negatively affected their children behavior and caused stress, mood changes or physical fatigue in their daily life. CONCLUSION: Our study shows that insomnia is most prevalent in individuals with autism with several consequences on children and family behavior and quality of life. As reported by parents, melatonin might be helpful for sleep disturbances in these children and the causes of restless sleep need further investigations.

Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review.

BACKGROUND: Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects). PATIENTS AND METHODS: We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected. RESULTS: 497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed. CONCLUSIONS: Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG.

Motor, epileptic, and developmental phenotypes in genetic disorders affecting G protein coupled receptors-cAMP signaling.

Over the last years, a constantly increasing number of genetic diseases associated with epilepsy and movement disorders have been recognized. An emerging group of conditions in this field is represented by genetic disorders affecting G-protein-coupled receptors (GPCRs)-cAMP signaling. This group of postsynaptic disorders includes genes encoding for proteins highly expressed in the central nervous system and involved in GPCR signal transduction and cAMP production (e.g., GNAO1, GNB1, ADCY5, GNAL, PDE2A, PDE10A, and HPCA genes). While the clinical phenotype associated with ADCY5 and GNAL is characterized by movement disorder in the absence of epilepsy, GNAO1, GNB1, PDE2A, PDE10A, and HPCA have a broader clinical phenotype, encompassing movement disorder, epilepsy, and neurodevelopmental disorders. We aimed to provide a comprehensive phenotypical characterization of genetic disorders affecting the cAMP signaling pathway, presenting with both movement disorders and epilepsy. Thus, we reviewed clinical features and genetic data of 203 patients from the literature with GNAO1, GNB1, PDE2A, PDE10A, and HPCA deficiencies. Furthermore, we delineated genotype-phenotype correlation in GNAO1 and GNB1 deficiency. This group of disorders presents with a highly recognizable clinical phenotype combining distinctive motor, epileptic, and neurodevelopmental features. A severe hyperkinetic movement disorder with potential life-threatening exacerbations and high susceptibility to a wide range of triggers is the clinical signature of the whole group of disorders. The existence of a distinctive clinical phenotype prompting diagnostic suspicion and early detection has relevant implications for clinical and therapeutic management. Studies are ongoing to clarify the pathophysiology of these rare postsynaptic disorders and start to design disease-specific treatments.

The Role of Vitamin D in Sleep Disorders of Children and Adolescents: A Systematic Review.

This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone health of the human body, but it also appears to play a role in sleep. The goal of our review is to examine the association between vitamin D and sleep disorders in children and adolescents. We summarize the evidence about the role and the mechanism of action of vitamin D in children and adolescents with sleep disorders such as insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and other sleep disorders. Systematic electronic database searches were conducted using Pubmed and Cochrane Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The studies that met the established inclusion criteria were analyzed and compared. Results suggest a strict relationship between vitamin D deficiency in children and sleep disorders. There is evidence that vitamin D is implicated in the different neurochemical mechanisms involved in sleep regulation and mainly in the serotonergic and dopaminergic pathways. This might be responsible for the association of vitamin D deficiency and restless sleep, sleep hyperhidrosis, OSA, and RLS.