Management of children with febrile seizures: a Greek nationwide survey.

The purpose of this study was to investigate knowledge, principles, and practices concerning the management of children with febrile seizures among pediatricians in Greece. A cross-sectional study was performed across Greece. Pediatricians completed an anonymous and voluntary 11-item questionnaire about their knowledge, attitudes, and practices with respect to the management of febrile seizures; the survey also collected demographic data. It was first administered in paper form in October 2017. This was followed by an online survey performed between June and August of 2018 and publicized by medical boards across Greece. Descriptive statistics and comparisons between groups were conducted with the significance level set at p ≤ 0.05. We recorded 457 responses. Pediatricians admitted to modifying their advice to the parents of children with febrile seizures by suggesting more "aggressive" fever management at low temperatures or systematically (63%), referral to a specialist after any episode of febrile seizures (63%), or hospitalization in a subsequent episode (67%), even though 72% admitted these practices were of no efficacy. Almost one in three pediatricians (28%) believed aggressive management of fever could delay the onset of febrile seizures; increasing age was associated with this perception. A minority (28%) would make parents aware of febrile seizures before a first episode regardless of family history; 38% would do so in the event of family history. CONCLUSIONS: Several pediatricians in Greece use outdated and ineffective practices for the management of febrile seizures, despite the availability of updated evidence-based guidelines. Further training of practitioners is needed to bridge this gap. WHAT IS KNOWN: •Aggressive management of fever at low temperatures with antipyretics, referral to a neurologist, and hospitalization are not supported by evidence or recent guidelines on childhood febrile seizures. •Febrile seizures are especially disturbing to uninformed parents, who may be inclined to pursue aggressive but ineffective treatments as a result. WHAT IS NEW: •Pediatricians in Greece use non-evidence-based practices for the management of febrile seizures, even when they are aware that these practices are not effective. •Older age increases the likelihood that a pediatrician will pursue guideline non-compliant practices in Greece. At the same time, physicians with over 20 years of experience are more likely to inform parents in advance about febrile seizures.

Immunogenicity and side-effects of the inactivated hepatitis A vaccine in periodic fever, aphthous stomatitis, pharyngitis, and adenitis patients.

The aim of this study was to compare the immunogenicity and side-effects of hepatitis A virus (HAV) vaccination between periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) patients and healthy controls who have not been previously exposed to HAV. A prospective observational study was carried out of 28 PFAPA patients and 76 controls who received two doses of the vaccine. Immunogenicity was expressed as seroconversion and seroprotection rates; mean HAV-immunoglobulin G concentration was measured at 0, 1, 7 and 18 months. Side-effects were defined as incidence of adverse events and the effect of vaccination on PFAPA symptoms. All participants were seronegative and seroconverted at 1 month. One month after primary vaccination, 92.9% of PFAPA patients and 77.6% of the controls attained seroprotection, while the rates increased to 100% and 96.1%, respectively, 1 month after the second dose. Seroprotection rates remained adequate 1 year after completion of vaccination. In conclusion, two doses of the inactivated HAV vaccine are well-tolerated and effective in children with PFAPA.

Immunogenicity and safety of the inactivated hepatitis A vaccine in children with juvenile idiopathic arthritis on methotrexate treatment: a matched case-control study.

OBJECTIVES: To describe the immunogenicity and side effects of immunisation against hepatitis A virus (HAV) in JIA patients on methotrexate treatment, who have not been previously exposed to HAV. METHODS: Case-control study performed in JIA patients and healthy controls matched on age and gender. The subjects received two doses of inactivated anti-HAV vaccine (720 mIU/ml) intramuscularly at 0 and 6 months. Seroconversion, seroprotection rates and anti-HAV-IgG titres were measured at 1, 7 and 18 months. Children were monitored for adverse events. RESULTS: 83 JIA patients and 76 controls were enrolled in the study. At one month, seroprotection rates were lower in children with, as compared to those without JIA (48.2% vs. 65%; p=0.05). At 7 and 18 months, rates of seroprotection rose significantly and were similar in both groups. The titre of anti-HAV-IgG was lower in children with JIA than healthy children at all time points (p<0.001). Vaccines were well tolerated. CONCLUSIONS: Two doses of inactivated HAV vaccine were well tolerated and immunogenic in most immunosuppressed children with JIA; however, a single dose of HAV vaccine was insufficient to induce seroprotection in half of the patients. Further studies are required to analyse the long-term immunity against HAV in this population and optimal HAV immunisation regimen.

Insertion of an extra copy of Xq22.2 into 1p36 results in functional duplication of the PLP1 gene in a girl with classical Pelizaeus-Merzbacher disease.

BACKGROUND: Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder characterized by nystagmus, hypotonia, ataxia, progressive spasticity, and cognitive decline. PMD classically results from a duplication of a genomic segment encompassing the entire PLP1 gene. Since the PLP1 gene is located in Xq22, PMD affects mostly boys. METHODS AND RESULTS: Here we report the case of a girl with typical PMD. Copy number analysis of the PLP1 locus revealed a duplication of the entire gene and FISH analysis showed that the extra copy of the PLP1 gene was actually inserted in chromosome 1p36. This insertion of an additional copy of PLP1 in an autosome led to a functional duplication irrespective of the X-inactivation pattern. Subsequent overexpression of PLP1 was the cause of the PMD phenotype observed in this girl. Further sequencing of the breakpoint junction revealed a microhomology and thus suggested a replication based mechanism (such as FoSTeS or MMBIR). CONCLUSION: This case emphasizes the susceptibility of the PLP1 locus to complex rearrangement likely driven by the Xq22 local genomic architecture. In addition, careful consideration should be given to girls with classical PMD clinical features since they usually experience complex PLP1 genomic alteration with a distinct risk of inheritance.

Postinfectious Rhabdomyolysis in a 5-Year-Old Boy: When to Look a Little Deeper.

UNLABELLED: We report on a 5-year-old boy with recurrent severe postinfectious rhabdomyolysis who, after systematic stepwise evaluation, was found to have the adult form of carnitine palmityl transferase II (CPT II) deficiency directly by blood mutation analysis. Timely diagnosis of CPT II deficiency in this case prevented further potentially devastating episodes of rhabdomyolysis by avoiding triggering factors. CONCLUSION: Although most cases of rhabdomyolysis are nonrecurrent and benign, a metabolic myopathy, such as CPT II deficiency, should be suspected in children with episodic muscle necrosis and paroxysmal myoglobinuria.

Combined Central and Peripheral Demyelination (CCPD) Associated with MOG Antibodies: Report of Four New Cases and Narrative Review of the Literature.

Background/Objectives: Myelin oligodendrocyte glycoprotein (MOG) is exclusively expressed in the central nervous system (CNS) and is found on the outer surface of oligodendrocytes. Antibodies to MOG are associated with CNS demyelination, whereas peripheral nervous system (PNS) demyelination is seldom reported to be related to MOG-IgG. Methods: The database of patients seen in our neurological academic center was searched for MOG-IgG seropositivity and concomitant demyelinating polyneuropathy. For the purpose of the review, in March 2024, we searched for case reports and case series in the following databases: PubMed, Scopus, Cochrane, and ScienceDirect. Inclusion criteria were MOG-IgG seropositivity and demyelinating polyneuropathy. Exclusion criteria were type of publication other than case reports and case series, unconfirmed diagnosis of demyelinating polyneuropathy, and other diseases causing demyelination in either the CNS or PNS. Critical appraisal of the selected case reports and case series was realized by JBI. Results: Four new cases were identified with MOG-IgG and confirmed demyelinating polyneuropathy. This review identified 22 cases that have been published since 2018. Clinical, imaging, neurophysiological, and immunological characteristics, as well as treatment options and outcomes are presented and compared to those of other cases with combined central and peripheral demyelination (CCPD). Conclusions: The pathogenetic mechanism is unclear; thus, different hypotheses are discussed. New case reporting and large cohort studies will help further the exploration of the underlying mechanism and guide more effective therapeutic interventions.

Markedly decreased antibody titers against hepatitis B in previously immunised children presenting with juvenile idiopathic arthritis.

OBJECTIVES: Hepatitis B is a vaccine preventable disease with intermediate endemicity in Greece. Patients with juvenile idiopathic arthritis (JIA) on immunomodulating therapy are prone to infection or reactivation of hepatitis B virus (HBV). The aim of this study is to define the immune status against HBV in children newly-diagnosed with JIA. METHODS: Case-control prospective study including 89 JIA patients and 89 controls matched for age and gender. Eighty-nine JIA patients were included in the study (22 males), with a mean age of 6.8 years. Sera were tested for hepatitis B surface antigen, hepatitis B core antibody, and anti-HBs. Patients with anti-HBs titers ≥10 IU/L were considered immune. Data were analysed with SPSS 18.0 version. RESULTS: In the JIA group 55% were HBV immune (anti-HBs level ≥10 IU/L) while in the control group 92% were immune against HBV (p<0.001). Antibody levels in the patient group were significantly lower compared to the control group. The mean concentration of anti-HBs levels in JIA patients was 18.3 IU/L versus 82.6 IU/L in the control group (p<0.001). CONCLUSIONS: Antibody titers against HBV in fully vaccinated JIA patients due to start treatment are significantly lower compared to matched healthy children in this study. Diagnosis of JIA and older age were associated with the absence of protective antibodies. Although there is no evidence to support the introduction of a booster HBV dose in healthy children who mount low antibody response following immunisation, further studies are required to address this question in patients with JIA.

A Co-diagnosis of Crohn Disease and Autoimmune Diabetes in an Adolescent Patient.

Inflammatory bowel disease (IBD) is a lifelong, immune-mediated disorder that often occurs in childhood and is becoming increasingly common worldwide. Diagnosis of IBD in children remains difficult due to the spectrum of symptoms, including gastrointestinal and extraintestinal manifestations. Type 1 diabetes mellitus (T1D) is one of the most common autoimmune diseases in children and adolescents. Classic manifestations of T1D in young people include polyuria, polydipsia, abdominal pain, weight loss, and ketoacidosis. However, children with autoimmunity of pancreatic ß-cells may remain euglycemic and asymptomatic for many years. An accurate and prompt diagnosis of IBD and T1D is particularly important in children because they can negatively affect growth, psychosocial function and overall well-being. We present a case in which a previously healthy child was co-diagnosed with Crohn disease and T1D during a routine pediatric evaluation in the outpatient clinic of a peripheral secondary hospital.

Functional and behavioral outcome of bacterial meningitis in school-aged survivors.

BACKGROUND: Bacterial meningitis is a serious infection with high morbidity and a significant risk for neurological and functional sequelae. The purpose of this study was to assess children and teenagers with a history of bacterial meningitis for functional and behavioral problems. METHODS: Thirty children and teenagers who suffered bacterial meningitis beyond the age of 6 months were compared against 30 healthy controls for functional and behavioral problems. Both groups were assessed using the Child Behavior Checklist by Achenbach for abilities and behavioral problems. RESULTS: No significant difference was found between the two groups. CONCLUSION: School-aged survivors of bacterial meningitis beyond the first 6 months of life have a very good prognosis with regards to competence and behavior.

HLA-DRB1 allele impact on pediatric multiple sclerosis in a Hellenic cohort.

BACKGROUND: Pediatric-onset multiple sclerosis (POMS) is considered a complex disease entity with many genetic and environmental factors implicated in its pathogenesis. Linkage studies in Caucasian adult populations consistently demonstrate the major histocompatibility complex and its HLA (human leukocyte antigen) polymorphisms as the genetic locus most strongly linked to MS. OBJECTIVE: To investigate the frequencies and possible clinical and imaging correlations of HLA-DRB1 alleles in a Hellenic POMS sample. METHODS: Fifty POMS patients fulfilling the IPMSSG (International Pediatric Multiple Sclerosis Study Group) criteria were enrolled using 144 adult-onset MS (AOMS) patients and 246 healthy controls for comparisons. HLA genotyping was performed with standard low-resolution sequence-specific oligonucleotide (SSO) techniques. Clinical and imaging correlations with specific HLA-DRB1 alleles were also examined. RESULTS: The HLA-DRB1*03 genotype was significantly higher in POMS patients compared to both the AOMS population (26% vs. 12.5%, p = 0.042) and the general population (26% vs. 12.6%, p = 0.004). HLA-DRB1*03-positive POMS patients had significantly more relapses (6.9 ± 4.9 vs. 4.2 ± 4.4, p = 0.005) and more thoracic spinal cord lesions than HLA-DRB1*03-negative patients (61.5% vs. 27%, p = 0.043). CONCLUSION: In our Hellenic population, HLA-DRB1*03 allele confers increased risk for POMS and it is also correlated with possibly increased disease activity, expanding the existing knowledge on HLA associations and POMS.

Evaluation of Genotypes and Epidemiology of Spinal Muscular Atrophy in Greece: A Nationwide Study Spanning 24 Years.

BACKGROUND: Promising genetic treatments targeting the molecular defect of severe early-onset genetic conditions are expected to dramatically improve patients' quality of life and disease epidemiology. Spinal Muscular Atrophy (SMA), is one of these conditions and approved therapeutic approaches have recently become available to patients. OBJECTIVE: Analysis of genetic and clinical data from SMA patients referred to the single public-sector provider of genetic services for the disease throughout Greece followed by a retrospective assessment in the context of epidemiology and genotype-phenotype associations. METHODS: Molecular genetic analysis and retrospective evaluation of findings for 361 patients tested positive for SMA- and 862 apparently healthy subjects from the general population. Spearman rank test and generalized linear models were applied to evaluate secondary modifying factors with respect to their impact on clinical severity and age of onset. RESULTS: Causative variations- including 5 novel variants- were detected indicating a minimal incidence of about 1/12,000, and a prevalence of at least 1.5/100,000. For prognosis a minimal model pertaining disease onset before 18 months was proposed to include copy numbers of NAIP (OR = 9.9;95% CI, 4.7 to 21) and SMN2 (OR = 6.2;95% CI, 2.5-15.2) genes as well as gender (OR = 2.2;95% CI, 1.04 to 4.6). CONCLUSIONS: This long-term survey shares valuable information on the current status and practices for SMA diagnosis on a population basis and provides an important reference point for the future assessment of strategic advances towards disease prevention and health care planning.

Intracranial hypertension in pediatric patients with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) remains one of the most common malignancies of childhood. Between April 1999 and August 2004, 9 of 207 patients treated at a Tertiary Oncology Service for ALL presented with Intracranial Hypertension (IH). Seven of the patients met the diagnostic criteria for Idiopathic Intracranial Hypertension (IIH). Four of the patients were treated with cerebrospinal fluid (CSF) drainage alone and four required Acetazolamide. Two of the four patients who were treated with Acetazolamide required subsequently a lumbar-peritoneal (LP) shunt. One patient succumbed to his disease before receiving any specific treatment.

Rituximab as Rescue Therapy for Aggressive Pediatric Multiple Sclerosis.

Multiple sclerosis is a chronic, debilitating disease. Almost one in ten patients with MS has a history of disease onset during childhood. Although numerous therapeutic options exist for adult MS, the available treatments for pediatric patients are still limited. One of the emerging therapies is rituximab, a monoclonal anti-CD20 chimeric antibody that can deplete the CD20+ lymphocyte populations. A 12-year-old boy presented with ataxia, paresthesias, and headache while his brain MRI showed numerous T2 contrast-enhancing lesions. Gamma globulin, steroids, and cyclophosphamide failed to intercept his disease, and he progressed to a rapid clinical and radiological deterioration. Treatment with rituximab reversed the disease course in a dramatic fashion, leading to complete remission.