A peculiar family with recurrent self-limited epileptic syndrome and associated developmental disorders in six girls.

We describe a complex family with two couples (two sisters who married two brothers) with consistent social and neuropsychiatric problems, originally from Sardinia. Each couple had three daughters, which shared electroclinical epileptic syndrome and developmental disorders. All patients suffered from mild to moderate intellectual disability, speech difficulties and behavioural disorders. Four out of six patients had epilepsy onset between 3 and 4 years of age. The epileptic history almost reflected the typical clinical course of a self-Limited Focal Epilepsy of Childhood. However, our patients don't have the complete features characteristic of one of the four specific self-Limited Focal Epilepsies of Childhood; a progressive evolution into a Developmental and/or Epileptic Encephalopathy with spike-wave activation in sleep was observed in the two older sister of the first family, which developed more severe developmental disorder too. In the other epileptic patients, improvement of EEG pattern was not coincident with an improvement of the developmental disorders. Brain MRI, performed in three patients, showed normal findings. Genetic analysis carried out so far (SNP-array, study of Runs of homozygosity, FMR1 triplet-repeat primer-PCR assay, Next Generation Sequencing based gene panel for epilepsy and neurodevelopmental disorders and Exome Sequencing), did not provide useful elements for an aetiological diagnosis.

De novo Absence Status Epilepticus in a pediatric cohort: Electroclinical pattern in a multicenter Italian patients cohort.

PURPOSE: Absence Status epilepticus (AS) is a form of Non Convulsive Status Epilepticus defined as a prolonged, generalized and non-convulsive seizure, with an altered content of consciousness. We aim to describe a group of healthy children, who presented recurrent and unprovoked de novo AS as the only manifestation of their epilepsy, with an excellent response to antiepileptic drugs. METHOD: We retrospectively reviewed the electroclinical and genetic features of 13 pediatric patients, referring to our epilepsy centers from 2005 to 2019, on the following criteria: (1) regular psychomotor development, (2) one or more unprovoked AS as the only epileptic manifestation, (3) normal blood testing, (4) normal neuroimaging, (5) EEG recording, (6) available follow-up (1-14 years). RESULTS: Patients are 7 females and 6 males, aged 7-22, with a mean age at AS onset of 9,3 years. All of them started an antiepileptic therapy, with an excellent response to Valproic Acid (VPA) or Ethosuximide (ETS). 5 patients did not start the therapy immediately after the first AS and they presented recurrent AS (from 2 to 4 episodes). 10 of them performed aCGH, karyotype, NGS panel or Whole Exome Sequencing. CONCLUSIONS: We suggest that de novo AS may be a well-defined age-related and self-limited epilepsy syndrome, with a good prognosis and excellent response to therapy, but it comes with a high risk of relapsing if not adequately treated with antiepileptic drugs.

Novel NALCN biallelic truncating mutations in siblings with IHPRF1 syndrome.

Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1) is a severe autosomal recessive neurologic disorder with onset at birth or in early infancy. It is caused by mutations in the NALCN gene that encodes a voltage-independent, cation channel permeable to NM, K+ and Ca2+ and forms a channel complex with UNCSO and UNC79. So far, only 4 homozygous mutations have been found in 11 cases belonging to 4 independent consanguineous families. We studied a Sardinian family with 2 siblings presenting dysmorphic facies, hypotonia, psychomotor retardation, epilepsy, absent speech, sleep disturbance, hyperkinetic movement disorder, cachexia and chronic constipation. Polymorphic generalized seizures started at 4 and 6 years, respectively. Anti-epileptic drugs (AEDs) therapy was efficient for female proband's epilepsy, but the male still has weekly seizures. Whole exome sequencing identified 2 novel truncating mutations in NALCN allowing to assess the clinical phenotype to IHPRF1. This is the fifth family reported worldwide, and these are the first European cases with IHPRF1 syndrome with biallelic truncating mutations of NALCN.

Electroclinical findings and long-term outcomes in epileptic patients with inv dup (15).

OBJECTIVE: To define the electroclinical phenotype and long-term outcomes in a cohort of patients with inv dup (15) syndrome. MATERIAL AND METHODS: The electroclinical data of 45 patients (25 males) affected by inv dup (15) and seizures were retrospectively analysed, and long-term follow-up of epilepsy was evaluated. RESULTS: Epilepsy onset was marked by generalized seizures in 53% of patients, epileptic spasms in 51%, focal seizures in 26%, atypical absences in 11% and epileptic falls in 9%. The epileptic syndromes defined were: generalized epilepsy (26.7%), focal epilepsy (22.3%), epileptic encephalopathy with epileptic spasms as the only seizure type (17.7%) and Lennox-Gastaut syndrome (33.3%). Drug-resistant epilepsy was detected in 55.5% of patients. There was a significant higher prevalence of seizure-free patients in those with seizure onset after the age of 5 years and with focal epilepsy, with respect to those with earlier epilepsy onset because most of these later developed an epileptic encephalopathy (69.2% vs 34.4%; P = .03), usually Lennox-Gastaut Syndrome in type. In fact, among patients with early-onset epilepsy, those presenting with epileptic spasms as the only seizure type associated with classical hypsarrhythmia achieved seizure freedom (P < .001) compared to patients with spasms and other seizure types associated with modified hypsarrhythmia. CONCLUSIONS: Epilepsy in inv dup (15) leads to a more severe burden of disease. Frequently, these patients show drug resistance, in particular when epilepsy onset is before the age of five and features epileptic encephalopathy.

Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study.

PURPOSE: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions. PATIENTS AND METHODS: This Italian multicenter retrospective observational study was performed in 16 paediatric epilepsy centres. Inclusion criteria were: (i) ≤18 years of age, (ii) history of refractory epilepsy, (iii) a follow-up ≥5 months of PER add-on therapy. Exclusion criteria were: (i) a diagnosis of primary idiopathic generalized epilepsy, (ii) variation of concomitant AEDs during the previous 4 weeks. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline. RESULTS: 62 patients suffering from various refractory epilepsies were included in this study: 53% were males, the mean age was 14.2 years (range 6-18 years), 8 patients aged <12 years. Mean age at epilepsy onset was 3.4 years and the mean duration of epilepsy was 10.8 years (range 1-16), which ranged from 2 seizures per-month up to several seizures per-day (mean number=96.5). Symptomatic focal epilepsy was reported in 62.9% of cases. Mean number of AEDs used in the past was 7.1; mean number of concomitant AEDs was 2.48, with carbamazepine used in 43.5% of patients. Mean PER daily dose was 7.1mg (2-12mg). After an average of 6.6 months of follow-up (5-13 months), the retention rate was 77.4% (48/62). The response rate was 50%; 16% of patients achieved ≥75% seizure frequency reduction and 5% became completely seizure free. Seizure aggravation was observed in 9.7% of patients. Adverse events were reported in 19 patients (30.6%) and led to PER discontinuation in 4 patients (6.5%). The most common adverse events were behaviour disturbance (irritability and aggressiveness), dizziness, sedation and fatigue. CONCLUSION: PER was found to be a safe and effective treatment when used as adjunctive therapy in paediatric patients with uncontrolled epilepsy.

Neuropsychological, psychiatric, and physical manifestations in 149 members from 18 fragile X families.

One hundred forty-nine subjects from 18 families with fragile X [fra(X)] syndrome were evaluated for their neuropsychological, psychiatric, and physical characteristics. The 36 fra(X) males had intelligence quotients ranging from less than 20 to 61, which prevented the delineation of a reliable neuropsychological profile. Behaviour fitted DSM-III-R and ADI diagnostic criteria of autism in only 2 subjects, both with very low intelligence level (IQ less than 20). Of 36 heterozygotes (HZ), 22 had an IQ between 20 and 80 and 14 between 81 and 99. The neuropsychological profile of the latter was compared with IQ-age-environment-matched 14 normal females and 14 normal males. Significantly poorer results in HZ were found on immediate digit memory and on Raven's progressive matrices (a visuo-spatial test of logical capabilities). The latter result, in conjunction with those results on the Bender visual-motor gestalt test and on some WAIS subtests, suggests a frequent deficit in spatial capabilities in such subjects. Such results tended to be confirmed by the profiles of the 22 HZ with IQ 20-80. No psychiatric abnormalities were found in HZ, except in one subject with IQ less than 20 which fitted DSM-III-R and ADI criteria for autism. Typical physical manifestations, especially cranio-facial, were more frequently present in the HZ group with lower IQ. Subnormal IQ was probably the most reliable abnormality for the detection of HZ in 49 females at 50% and 25% risk of heterozygosity.

Polymicrogyria: a case detected by MRI.

We report a 3-year-old child affected by severe encephalopathy, partial seizures with early onset and microgyria whom polymicrogyria was detected by means of magnetic resonance imaging (MRI). We believe that MRI first allow an early and confident in vivo diagnosis of this severe and probably not so rare condition.

Síndrome de Frey / Frey's syndrome

Se revisan 100 historias clínicas de pacientes operados de tumores primarios de las glándulas parótidas. En esta revisión se encontraron 10 casos afectados del síndrome de Frey. Se describen la fisiopatología y la localización, y se da a conocer el tratamiento médico o quirúrgico que se puede utilizar en estos casos. Se destaca como elemento importante para detectar el síndrome de Frey, el seguimiento de los pacientes operados de tumores de las glándulas parótidas(AU)

Pseudoquistes del páncreas: estudio estadístico / Pseudocysts of the pancreas. Statistical study

Se estudian 30 pacientes con pseudoquistes pancreáticos ingresados en 9 hospitales del país. De ellos, 15 eran hombres y 15 mujeres, con predominio de la enfermedad en la quinta década de la vida (30 porciento). Tuvieron como origen la pancreatitis el 63,3 porciento de los enfermos y los traumatismos el 36,3 porciento. Aproximadamente en la mitad de los pacientes, el diagnóstico se efectuó en los tres primeros meses del episodio agudo. Las manifestaciones clínicas principales fueron el dolor abdominal (83,3 porciento), el tumor palpable (76,6 porciento) y las náuseas con o sin vómitos (66,6 porciento). Los estudios de mayor valor para el diagnóstico de la enfermedad fueron la ultrasonografía (96,1 porciento) y la tomografía axial computadorizada (92,3 porciento)(AU)

Flunarizine in therapy-resistant infantile epilepsies.

An open add-on trial with flunarizine has been carried out in 27 cases of therapy resistant infantile epilepsies: 15 partial and 12 generalized epilepsies. Etiology was an hypoxic-ischemic encephalopathy (HIE) in 13 cases, cerebral malformations in 10 cases and 4 various prenatal and perinatal cases. After a 2 months baseline period, flunarizine was given in addition to the previous therapy in a 5 mg once daily dose. A single blind versus placebo study was carried out in another series of 16 cases. Better results were found in HIE cases than in malformative cases, and in cases with perinatal HIE than in cases with prenatal hypoxic encephalopathy. The improvement in symptomatic generalized epilepsies was more evident than in symptomatic partial epilepsies. Drowsiness was the only side effect reported.

[Flunarizine in drug-resistant epilepsies of childhood and adolescence]. / La flunarizina nelle epilessie farmaco-resistenti dell'infanzia e dell'adolescenza.

Therapeutic effects of flunarizine have been studied on 26 patients, aged from 9 months to 17 years, suffering for epilepsies resistant to common anticonvulsant treatment, despite proper plasmatic levels of drugs. All the cases were monitored with monthly clinical and EEG controls, neuropsychological evaluations and monitoring antiepileptic drugs plasmatic levels. At first, a study was performed on an intra-patient basis: after a basal observation during two months, an open clinical trial was started, using for three months flunarizine 5 mg a day in patients weighing over 10 kg, and 5 mg every two days in children weighing less than 10 kg. Later on, a simple blind clinical trial has been performed on 16 patients, using flunarizine or placebo for three months. The results, obtained in resistant epilepsy of children and adolescent, showed that flunarizine induced in 47.6% of cases a significant reduction of critical (stroke) frequency and intensity, together with normalization of sleeping-waking rhythm, and amelioration of attention performances (vigilance, reactivity, environmental participation). The only side-effect, noticed in 23.8% of cases, was a light diurnal sleepiness, spontaneously regressing after a few days of treatment.

Esplenectomía: Indicaciones, morbilidad y letalidad en 80 casos revisados / Splenectomy: suggestions, morbility and mortality in 80 revised cases

Se presentó el estudio de 80 esplenectomías realizadas en un período de 5 años en el Hospital Provincial Docente de Santa Clara, Las Villas y en el Hospital General de Placetas; y se observó que la mayor incidencia se refiere a la rotura esplénica por trauma. Se pone de manifiesto la importancia de la punción abdominal en el diagnóstico precoz del hemoperitoneo traumático, y se sugieren medidas prifilácticas para disminuir la incidencia de la lesión accidental del brazo. Secomunica el resultado satisfactorio obtenido en el hiperesplenismo, las derivaciones esplenorrenales y los quistes esplénicos; y se plantea que la laparoscopia constituyó un método auxiliar valioso en el diagnóstico de las tumoraciones del hipocondrio izquierdo. Se observa que la mayor mortalidad recayó en el grupo de los politraumatizados (AU)