Prospective study of febrile seizures: prognostic factor for epilepsy occurence

Following a first febrile seizure (FS) 2-7% of children experience a subsequent unprovoked seizure, a risk four times the risk in the general population. The increased risk for later unprovoked seizures is substantially greater among children with neurologic abnormalities present from birth than among children without such abnormalities. For most children with febrile seizures (i.e., those with simple febrile seizures), the risk of unprovoked seizure is only slightly increased. The present study was carried out during the period 2002-2005 in order to identify the prognostic factors that can lead the child with febrile seizures to epilepsy. This study is a prospective one and included 501 children with a first febrile seizure, aged from 3 months to 5 years old, who were followed for a median time of 30 months ± 8 months. According to the protocol, we gathered information about prenatal and perinatal history of each child, family history of FS and epilepsy, age at the time of the initial febrile convulsion, dates of subsequent febrile convulsions, presence or absence of focal features (including Todd’s paresis), duration of the febrile seizure and whether repeated episodes within the same febrile illness occurred, height and duration of fever prior to the seizure, cause of fever and their frequency during the follow-up period. At the time of the first FS a detailed history was received and physical, developmental and neurologic assessments were conducted by a paediatric neurologist. All children had an electroencephalographic recording (EEG) as soon as they were afebrile, after their first FS and each FS recurrence. We gathered information not only from the first febrile seizure but also from the recurrences. In our study the percentage of subsequent epilepsy in children with first FS was estimated at least 5.4%. Univariate analysis of our data showed that prognostic factors for the occurrence of epilepsy in children with febrile seizures are: family history of epilepsy (especially maternal preponderance), complex febrile seizures at the first crisis and at recurrences, focality both at the first febrile seizure and at recurrences, duration of fever less than 12 hours prior to the first febrile seizure and multiple episodes of febrile seizures (≥ 4). Multivariate analysis revealed that the most powerful prognostic factors for epilepsy after FS are: age at onset of FS older than 3 years of age, family history of epilepsy, complex FS and multiple episodes of FS (more than four). As for the recurrences of FS multivariate analysis showed that, at the first and the second recurrence of FS focality and duration of fever less than 12 hours prior to the crisis had predictive value for the outcome of epilepsy. The combined effect of the two above factors increased the risk of epilepsy about 8,5 times. For the next recurrences (third, fourth, etc) the prognostic factor that remained was only focality and its prognostic value was multiplied. Children with four recurrences of FS had the risk of developing epilepsy increased about 30 times. The types of epilepsy that were preceded by febrile seizures were: generalized tonic-clonic epilepsy, focal epilepsy (including rolandic), generalized epilepsy febrile seizure plus syndrome, petit mal and myoclonic epilepsy. The majority of the focal epilepsies had a history of focal febrile seizures. The results from our study consist a prognostic index for the occurrence of epilepsy at each child with febrile seizure. Our research will be a very useful tool, with easily available clinical data, not only for the paediatric neurologist but also for the paediatrician.Το ποσοστό εμφάνισης επιληψίας μετά το πρώτο επεισόδιο πυρετικών σπασμών (ΠΣ) ανέρχεται σε 2-7%. Η παρούσα μελέτη διεξήχθη την περίοδο 2002-2005 με σκοπό να αναγνωρίσει τους προγνωστικούς παράγοντες που θα οδηγήσουν τα παιδί με ΠΣ σε επιληψία. Περιελήφθησαν σε προοπτική μελέτη 501 παιδιά με πρώτο επεισόδιο ΠΣ. Η πολυπαραγοντική ανάλυση έδειξε ότι οι πιο ισχυροί προγνωστικοί παράγοντες είναι: η ηλικία έναρξης ΠΣ (>3 ετών), το οικογενειακό ιστορικό επιληψίας, οι επιπλεγμένοι ΠΣ και τα πολλαπλά επεισόδια ΠΣ (περισσότερα από τέσσερα). Σε ότι αφορά τις υποτροπές των ΠΣ προγνωστική ισχύ είχαν η εστιακή σημειολογία που πολλαπλασιάζει την ισχύ της σε βάθος χρόνου και η μικρή διάρκεια του πυρετού (<12 ώρες) από το επεισόδιο για την 1η και 2η υποτροπή. Η έρευνά μας θα αποτελέσει ένα χρήσιμο εργαλείο για τον παιδίατρο με εύκολα διαθέσιμα κλινικά στοιχεία

Vaccination and neurological disorders

Active immunization of children has been proven very effective in elimination of life threatening complications of many infectious diseases in developed countries. However, as vaccination-preventable infectious diseases and their complications have become rare, the interest focuses on immunization-related adverse reactions. Unfortunately, fear of vaccination-related adverse effects can led to decreased vaccination coverage and subsequent epidemics of infectious diseases. This review includes reports about possible side effects following vaccinations in children with neurological disorders and also published recommendations about vaccinating children with neurological disorders. From all international published data anyone can conclude that vaccines are safer than ever before, but the challenge remains to convey this message to society

Not Just Loss-of-Function Variations: Identification of a Hypermorphic Variant in a Patient With a CDKL5 Missense Substitution

Background and objectives: CDKL5 deficiency disorder (CDD) is a neurodevelopmental encephalopathy characterized by early-onset epilepsy and impaired psychomotor development. Variations in the X-linked CDKL5 gene coding for a kinase cause CDD. Molecular genetics has proved that almost all pathogenic missense substitutions localize in the N-terminal catalytic domain, therefore underlining the importance for brain development and functioning of the kinase activity. CDKL5 also features a long C-terminal domain that acts as negative regulator of the enzymatic activity and modulates its subcellular distribution. CDD is generally attributed to loss-of-function variations, whereas the clinical consequences of increased CDKL5 activity remain uncertain. We have identified a female patient characterized by mild epilepsy and neurologic symptoms, harboring a novel c.2873C&gt;G nucleotide substitution, leading to the missense variant p.(Thr958Arg). To increase our comprehension of genetic variants in CDKL5-associated neurologic disorders, we have characterized the molecular consequences of the identified substitution. Methods: MRI and video EEG telemetry were used to describe brain activity and capture seizure. The Bayley III test was used to evaluate the patient development. Reverse transcriptase PCR was used to analyze whether the identified nucleotide variant affects messenger RNA stability and/or splicing. The X chromosome inactivation pattern was analyzed determining the DNA methylation status of the androgen receptor (AR) gene and by sequencing of expressed alleles. Western blotting was used to investigate whether the novel Thr958Arg substitution affects the stability and/or enzymatic activity of CDKL5. Immunofluorescence was used to define whether CDKL5 subcellular distribution is affected by the Thr958Arg substitution. Results: Our data suggested that the proband tends toward a skewed X chromosome inactivation pattern in favor of the novel variant. The molecular investigation revealed that the p.(Thr958Arg) substitution leads to a significant increase in the autophosphorylation of both the TEY motif and residue Tyr171 of CDKL5, as well as in the phosphorylation of the target protein MAP1S, indicating an hyperactivation of CDKL5. This occurs without evidently affecting the kinase subcellular distribution. Discussion: Our data provide a strong indication that the c.2873C&gt;G nucleotide substitution represents an hypermorphic pathogenic variation of CDKL5, therefore highlighting the importance of a tight control of CDKL5 activity in the brain

Large Cyst of Skene Gland: A Rare Perineum Mass

Objective In this report we present a rare case of a large cyst of Skene gland in a female patient with a palpable vaginal mass persisting for at least 2 years. Case Report A 67-year-old female admitted to the department of urology due to the presence of “a vaginal mass” for the past 2 years. A cyst of Skene's duct was suspected based on clinical manifestation and findings of magnetic resonance imaging showing an extensive cyst formation in the upper vaginal area and anterior to the urethra. Based on these findings, a decision for surgical removement of the cyst was made. The cyst was incised, drained, and marsupialized. The postoperative recovery was uneventful, and the patient was discharged on the second postoperative day. Conclusion High clinical suspicion is important to reach this rare diagnosis. Partial excision and marsupialization of the cyst is a simple procedure with low morbidity, without recurrence, and excellent results

Partial deletion of chromosome 6p causing developmental delay and mild dysmorphisms in a child: molecular and developmental investigation and literature search

Background The interstitial 6p22.3 deletions concern rare chromosomal events affecting numerous aspects of both physical and mental development. The syndrome is characterized by partial deletion of chromosome 6, which may arise in a number of ways. Case presentation We report a 2.8-year old boy presenting with developmental delay and mild dysmorphisms. High-resolution oligonucleotide microarray analysis revealed with high precision a 2.5 Mb interstitial 6p deletion in the 6p22.3 region which encompasses 13 genes. Conclusions Identification and in-depth analysis of cases presenting with mild features of the syndrome will sharpen our understanding of the genetic spectrum of the 6p22.3 deletion