Undernourishment and recurrent seizures early in life impair Long-Term Potentiation and alter NMDAR and AMPAR expression in rat hippocampus.

Undernourishment is a global issue, especially in developing countries, affecting newborns and children in a vulnerable period of brain development. Previous studies of undernourishment models suggested a relationship between undernourishment and epilepsy. The exposure to both undernourishment and recurrent seizures early in life appears to have detrimental effects on the developing brain. This study aims to investigate the neurobiological consequences of undernourishment and recurrent seizures exposure early in life, investigating Long-Term Potentiation (LTP) induction and gene expression of NMDA receptor subunits in the hippocampus during adulthood (P60). Animals were exposed to maternal deprivation protocol from P2 to P15 to control food intake in rat pups and Flurothyl-induced seizures from P7 to P10. Electrophysiological records of hippocampal slices were recorded and gene expression of NR1A, NR2A, NR2B, NR2C, NR2D and BDNF were investigated. Animals exposed to undernourishment or recurrent seizures failed to promote LTP after stimulation. Furthermore, seizure exposure early in life led to increased expression of hippocampal NR1A, NR2A, NR2B, NR2C and NR2D when compared to controls. Interestingly, when animals were exposed to undernourishment paradigm early in life, this upregulation of NDMA subunits was absent. In conclusion, our study showed impaired LTP after undernourishment and recurrent seizures early in life, together with differential expression of NDMA expression in the hippocampus during adulthood.

Peel flour of Passiflora edulis Var. Flavicarpa supplementation prevents the insulin resistance and hepatic steatosis induced by low-fructose-diet in young rats.

The increase in fructose consumption in the last decades has an important correlation with the growth of overweight population. Fructose is a monosaccharide found in fruits, vegetables and honey, however, it is widely used in processed food and beverages such as sweeteners. This monosaccharide is metabolized in the liver, so it can produce glucose, lactate, triglycerides, free fatty acids and uric acid, which are responsible for negative effects on the liver and extrahepatic tissues. One effect of the high consumption of fructose is the resistance to Insulin, which appears to be an important issue in the development of metabolic abnormalities observed in animals that were subjected to a high fructose diet. The population and, consequently, the market search for natural sources to manage metabolic abnormalities is increasing, but, adequate scientific proof still is necessary. The Passiflora edulis peel flour (PEPF) is a byproduct of the juice industry, and, represents an important source of fiber and bioactive compounds. The present study investigates the PEPF supplementation (30%) effects on insulin sensitivity, adiposity and metabolic parameters in young rats that were given beverages enriched with 10% of fructose for 8 weeks. Fructose intake induced insulin resistance, increased serum triglycerides levels, growth of fat deposits in the liver and widening of the diameter of adipocytes. In contrast, the group that received PEPF did not present such abnormalities, which could be related to the presence of fiber or bioactive compounds (phenolics compounds, e.g., caffeic acid and isoorientin) in its composition, as identified by analytical methods. Thus, for the first time, it has been demonstrated that PEPF supplementation prevents insulin resistance and hepatic steatosis induced by low-fructose-diet in young rats.

Nutrition and brain function: a multidisciplinary virtual symposium.

A few months ago, the Brazilian Society for Neuroscience and Behavior (SBNeC) promoted a "virtual symposium" (by Internet, under the coordination of R.C.A. Guedes) on "Nutrition and Brain Function". The discussions generated during that symposium originated the present text, which analyzes current topics on the theme, based on the multidisciplinary experience of the authors. The way the brain could be non-homogeneously affected by nutritional alterations, as well as questions like early malnutrition and the development of late obesity and hormone abnormalities were discussed. Also, topics like the role of essential fatty acids (EFAs) on brain development, increased seizure susceptibility and changes in different neurotransmitters and in cognitive performance in malnourished animals, as well as differences between overall changes in nutrient intake and excess or deficiency of specific nutrients (e.g. iodine deficiency) were analyzed. It was pointed out that different types of neurons, possibly in distinct brain structures, might be differently affected by nutritional manipulation, including not only lack-but also excess of nutrient intake. Such differences could help in explaining discrepancies between data on humans and in animals and so, could aid in determining the basic mechanisms underlying lesions or changes in brain function and behavior.

[Neurochristopathy in the differential diagnosis of newborn's apnea: case report]. / Neurocristopatia no diagnóstico diferencial das apnéias do recém nascido: relato de caso.

OBJECTIVE: to include neurocristopathy on the etiological workup of neonatal apneas and discuss the importance of polysomnography in this diagnosis. METHOD: case report and critical review of the literature. RESULTS: we report on a newborn that presented respiratory failure in the first hours of life associated to abdominal distention. Continuous ventilatory support was necessary, and the respiratory distress increased during sleep. After polysomnographic confirmation of hypoventilation the newborn was submitted to neuroradiolgic tests and colon byopsy, positive to Hirschsprung's disease. CONCLUSION: Neurocristopathy syndrome can have many different clinical expression, and sometimes the syndrome can be misdiagnosed. Polysomnography confirms central hypoventilation. This diagnosis should be considered in the newborn's persistent apnea workup.

Cerebral aneurysmal dilatation in an infant with perinatally acquired HIV infection and HSV encephalitis.

Although most children with human immunodeficiency virus (HIV) infection have neurological dysfunction, in childhood the incidence of symptomatic cerebrovascular disease is low. Cerebral aneurysmal arteriopathy in childhood AIDS has been reported in the past and considered to have a relatively long latency following the primary infection. We report a 1 month-old infant with congenitally acquired HIV infection, and herpes encephalitis; she presented a sudden cardiorespiratory arrest followed by coma and was found to have a giant saccular aneurysm of the left basilar artery. Literature review showed that cerebral aneurysmal artheriopathy is an unusual manifestation in newborns and infants and this case is possibly the youngest patient reported with aneurysma, herpes encephalitis and AIDS. The role of HIV and herpes simplex infections in the pathogenesis of this lesion is discussed.

[Seizures in the neonatal period] / Convulsões no período neonatal.

OBJECTIVE: To characterize and differentiate neonatal seizures from those that occur at different ages, based on a critical assessment of the available literature and also on the authors clinical experience. SOURCES: Literature review, including up-to-date and classical studies that helped us to better understand clinical, neurophysiological and physiopathological aspects related to seizures in the newborn. SUMMARY OF THE FINDINGS: The authors present clinical and electroencephalographic characteristics of neonatal seizures, discuss their classification, treatment and prognosis. CONCLUSIONS: Neonatal seizures have a distinct clinical pattern, which justifies the necessity of an appropriate classification. The etiology is predominantly symptomatic and multifactorial; the treatment should follow a routine protocol, and the prognosis seems to be closely related to etiology.

Polysomnography in neonatal seizures.

Seizures are one of the most frequent problems in the neonatal period, and are frequently associated with high mortality and morbidity rates. On the other hand, neonatal seizures may represent a first or even the only sign of central nervous system dysfunction. However, establishing the diagnosis of neonatal seizures poses several problems, and clinical observation is not sufficient in many cases. Neonatal polysomnography is a valuable tool both in the diagnostic and in the prognostic assessment of neonatal seizures. The present text reviews some technical aspects related to neonatal polysomnographies, and its usefulness in the area of suspected neonatal seizures. Moreover, some questions are raised regarding rhythmic discharges and their significance as a possible ictal and interictal epileptic pattern in the neonate.

Duration of rhythmic EEG patterns in neonates: new evidence for clinical and prognostic significance of brief rhythmic discharges.

OBJECTIVE: This study aimed at identifying the characteristics - especially the duration - of rhythmic discharges in neonatal EEG, and their association with clinical neonatal problems. Specifically, we aimed at testing the diagnostic and prognostic validity of using 10 s as minimal duration for defining electroencephalographic seizures. DESIGN AND METHODS: The polysomnographies of 340 neonates were reviewed, and episodes of rhythmic discharges were identified, analyzed, and quantified. The study sample was divided into 3 groups: one in which the maximal duration of rhythmic discharges was shorter than 10 s (brief rhythmic discharges, BRD), a second one in which there were rhythmic discharges longer than 10 s (long rhythmic discharges, LRD), and finally a group in which no rhythmic discharge was found (No-RD). These 3 groups of subjects were compared for the baseline and outcome clinical data. RESULTS: From the 340 neonates studied, 210 did not present any form of rhythmic discharge, 67 (19. 7%) had only BRD episodes, and 63 (18.5%) had at least one LRD episode. Prevalence of rhythmic discharges was low among healthy full term newborns, and was significantly higher among preterm and high-risk newborns. Electrophysiological characteristics of rhythmic discharges did not differ between healthy neonates and high-risk ones. Accompanying clinical manifestations were present in 26.3% of the LRD group, but also in 15.9% of the BRD group. The presence of BRD was significantly associated with leukomalacia and with hypoglycemia in the cross-sectional analysis of baseline data, and with an increased risk for abnormal neurodevelopmental outcome after a mean follow-up period of 47 months (adjusted relative risk=4.90, P<0.01). CONCLUSIONS: The present data demonstrate an association between BRD and clinical history of hypoxic-ischemic encephalopathy, especially when complicated by leukomalacia, and also with a prognosis of increased risk for abnormal neurodevelopmental outcome. The clinical and prognostic significance of isolated BRD justifies the need to include these brief episodes in future studies of neonatal seizures.

Differences in the dynamics of frontal sharp transients in normal and hypoglycemic newborns.

OBJECTIVE: This study focuses on the characteristics of frontal sharp transients (FST), a normal variant of neonatal EEG, in newborns with hypoglycemia. METHODS: The EEG from 20 newborns with symptomatic hypoglycemia were compared with a control group of normal newborns matched by conceptional age. The dynamics of these transients were evaluated concerning sleep stages. The density, type and bilateral synchrony of FST were also calculated. The results were compared in the two groups by Student's t test. RESULTS: When compared with controls, hypoglycemic newborns have increased density of frontal sharp transients in all sleep stages but less bilateral synchrony (P<0.05). FST density was even higher in small for gestational age newborns. CONCLUSIONS: The data suggests that normal patterns of neonatal EEG as FST can be influenced by systemic disturbances.

Congenital intramedullary tumor with neonatal manifestations.

The authors report on a 45-day-old boy with a congenital intramedullary tumor with clinical manifestations since birth. Neurologic examination disclosed severe bilateral lower-limb hypotonia and diplegia, with exacerbated deep tendon reflexes and clonus associated with severe pain at manipulation. Further evaluation of this patient included screening for infections, computed tomographic scan, myelography, and somatosensory evoked potentials. The definite diagnosis was a solid holocord astrocytoma. This report discusses a rare disorder in the neonatal period and makes other medical practitioners aware of this diagnosis. Previously published literature is also reviewed.

Subacute sclerosing panencephalitis. Clinical aspects and prognosis. The Brazilian registry.

Subacute sclerosing panencephalitis (SSPE) is an inflammatory neurodegenerative disease related to the persistence of measles virus. Although its frequency is declining because of measles eradication, we still have some cases being diagnosed. With the aim to describe epidemiological aspects of SSPE in Brazil, we sent a protocol to Child Neurologists around the country, 48 patients were registered, 27 (56%) were from the southeast region, 34 (71%) were male and 35 (73%) white, 27 (56%) had measles, 9 (19%) had measles and were also immunized, 7 (14%) received only immunization, 1 patient had a probable neonatal form. Mean time between first symptoms and diagnosis was 12 months (22 started with myoclonus or tonic-clonic seizures, 7 (14%) with behavioral disturbances); 36 patients (75%) had EEG with pseudoperiodic complexes. Follow up performed in 28 (58%) patients showed: 12 died, 2 had complete remission and the others had variable neurological disability. Our data shows endemic regions in the country, a high incidence of post-immunization SSPE and a delay between first symptom and diagnosis.

Association of misoprostol, Moebius syndrome and congenital central alveolar hypoventilation. Case report.

We report a case showing the association of Moebius syndrome, the use of misoprostol during pregnancy and the development of central congenital alveolar hypoventilation. Pathophysiological aspects of these three diseases are discussed and also the unfavorable prognosis of this association.

[Associated and prognosis in apparent life threatening events (ALTE)] / Patologias associadas e prognóstico de eventos com aparente risco de vida (ALTE).

OBJECTIVE: To verify the etiology and prognosis of ALTE in infancy and its possible relationship to Sudden Infant Death Syndrome (SIDS). METHODS: We studied a group of infants that presented ALTE episodes and were evaluated in our hospital. First we reviewed their clinical history and polysomnographies, then we sent a letter to the families with questions regarding the outcome. RESULTS: 56 patients were included. 92% had ALTE during their first 6 months and 83% in the first trimester. Symptomatic ALTE predominated (71%). The disease most frequently associated was gastroesophageal reflux, followed by neurological diseases. The follow up showed 51.5% of normal outcome, 4 children repeated ALTE, no cases of SIDS were registered. CONCLUSIONS: Our results showed that multifactorial etiologies can be associated to ALTE, and the outcome is generally related to the associated disease. We did not observe any relationship between ALTE and SIDS considering a predominantly symptomatic ALTE population.

[Phasic activity of REM sleep in newborns and infants and its relationship with apnea episodes]. / Atividade fásica do sono REM em recém-nascidos e lactentes e sua relação com episódios de apnéia.

When the apnea hypothesis turned to be an explanation for sudden infant death syndrome (SIDS) many authors tried to find if near-miss or apparent life-threatening events (ALTE) could be markers of SIDS. It was suggested that phasic REM activity is associated with increased respiratory neuron activity and prevents prolonged apnea in near-miss SIDS. In a previous retrospective study with newborns we did not confirm these results, nevertheless we had several babies with serious neurological disturbances. The aim of this study was to verify the relationship of phasic activity (rapid eyes movement and sucking bursts) with both apneic and non-apneic epochs during REM sleep. We studied 86 children referred for evaluation because they presented an ALTE during sleep or apneas. The subjects were divided in three groups by age (newborns, n = 31; 1-6 months, n = 48; and > 6 < 12 months, n = 7). They were all submitted to a clinical and neurological evaluation in order to detect possible etiological factors to the apneic episode. The polysomnograms (PS) consisted of EEG, submental EMG, electro-oculogram and cardiorespiratory monitoring. The records were made between 11 am and 15 pm for 2 or 3 hours. The electrodes were disposed in the 10-20 system. During one five-minutes epoch of REM sleep we verified the incidence of phasic activity (rapid eyes movement or sucking bursts) time locked to apneic episodes and compared with a similar duration non-apneic epoch. To evaluate the relationship of phasic activity with apneic and non-apneic eopchs we compared the incidence of rapid eyes movements and sucking bursts in each group. Our results showed that phasic activity of REM sleep (sucking bursts) seems to be more frequent in newborns in non-apneic epochs (p < 0.05). Between 1-6 months the number of rapid eyes movements were more frequent in non-apneic epochs (p = 0.001). In conclusion our findings suggest that phasic activity of REM sleep seems to be more evident in nonapneic epochs during the first six months of life. Although central apneas may have their origin in an intrinsic disturb of the respiratory control center they may be influenced by the phasic activity of REM sleep. The rapid eyes movements and sucking bursts may have a protection effect against apneas at least in the first 6 months of life. which is the predominant period for SIDS. We suggest that the excitatory driving related to generation of phasic activity in REM sleep may block or atenuate tonic inhibition of respiratory motoneuron and avoid apnea. It is still open for discussion the possible relation between failure of this protective mechanism and SIDS.

Polysomnographic quantification of bioelectrical maturation in preterm and fullterm newborns at matched conceptional ages.

We analyzed the relationship between normal neonatal EEG features and gestational age and conceptional age, and evaluated the normal aspects of EEG maturation in preterm babies compared to term babies. We report 46 newborns, divided into two groups. Group I consisted of 11 newborns with gestational age between 30 and 32 weeks, followed with weekly polysomnograms until they reach 42 weeks' conceptional age. Group II (control) consisted of 35 newborns with gestational ages of 34 weeks (n = 5), 36 weeks (n = 10), 38 weeks (n = 10) and 40 weeks (n = 10) evaluated with one polysomnogram in their first 24-48 h of life. In each examination one 5 min epoch in REM and NREM sleep was analyzed to quantify the number of delta brushes, the presence of frontal and temporal sharp transients, the presence of delta frontal rhythmic activity, the grade of concordance between EEG patterns and sleep stages, the percent of interhemispheric synchrony and the duration of interburst interval. The age dependent variability of the EEG patterns was evaluated during the subsequent weeks with group comparisons at weeks 34, 36, 38 and 40. Our results show that the number of delta brushes and the duration of the interburst interval decrease as gestational and conceptional age increase. The percent of interhemispheric synchrony increases with gestational and conceptional age. The presence of frontal sharp transients and delta frontal rhythmic activity suggest that the newborn is fullterm. The presence of temporal sharp transients suggest a preterm newborn. The degree of concordance between behavioral sleep patterns and EEG was more helpful in recognizing sleep stages than in estimating gestational or conceptional age. Although the EEG patterns were comparable between the groups at the same age, analyses of the behavioral patterns of concordance in NREM sleep showed that newborns in Group I had a more immature behaviour than newborns in Group II. Our results also suggest that extrauterine life of preterm babies does not seem to accelerate EEG maturation but may influence the acquisition of behavioral patterns during NREM sleep.

Vigabatrin in refractory childhood epilepsy. The Brazilian Multicenter Study.

Children, 47, with various types of severe drug-resistant epilepsy were entered into a prospective, add-on, open trial with vigabatrin. Patients with West syndrome and idiopathic generalized epilepsies were excluded. Seven children had the drug withdrawn, five because of increase in seizure frequency and two because of adverse effects. Drug efficacy, measured according to seizure type, showed a 100% decrease in seizure frequency in 18.6% of partial seizures and 17.3% of the generalized seizures. There was a higher than 50% decrease in 39.5% of partial and 60.8% of generalized seizures, and less than 50% decrease or increase in seizure frequency in 41.8% and 21.8% of partial and generalized seizures, respectively. Vigabatrin mean dosage during phase 3 was 63.6 mg/kg per day (S.D. = 30.5), ranging from 19.3 to 110.5 mg/kg per day. Parametric statistical analysis (Student's t-test) of seizure frequency between phases 1 and 3 showed a significant decrease in seizure frequency for partial (P = 0.022), and generalized seizures (P < 0.0001). Drug-related adverse effects were observed in 18/47 cases (38.3%), consisting mainly of irritability, hyperactivity, dizziness, somnolence and gastrointestinal symptoms.

[Value of EEG in the characterization and prognosis of neurological diseases in premature infants]. / Valor do EEG na caracterização e prognóstico de patologias neurológicas em recém-nascidos prematuros.

The importance of the EEG for the investigation of neurological diseases in the neonatal period has been largely discussed, since it is often the only way to approach cerebral function in newborns with severe pathologies or under drug effect. The present study was carried out with 85 newborns (NB) who presented perinatal dysfunctions and were submitted to neurological and electroencephalogram (EEG) or polysomnography (PS) evaluation. EEG/PS alterations, pathologies and prognosis were reported. The EEG were classified according to basal activity alterations, presence of paroxysmal activity and sleep stages organization and maturity. The most frequent pathology was perinatal asphyxia (40%) followed by intraventricular hemorrhage (HIV, 16%). The most frequent complaint for exam indication was apnea (71%) followed by convulsion (19%). Fifty-five percent of the exams exclusively required because apnea complaint were considered normal and out of all exams required because seizures only 31% were normal. The EEG alteration most frequently related to perinatal asphyxia, HIV and intrauterine growth delay was immaturity and in the NB with seizures immature EEG and abnormal paroxysms. Many different alterations were registered in the NB with nervous system infection. The EEG findings more correlated with unfavorable prognosis were isoelectricity and abnormal paroxysmal activity including positive sharp waves (100%).

Trihexyphenidyl and isoprinosine in the treatment of subacute sclerosing panencephalitis.

Six cases of subacute sclerosing panencephalitis (1 stage I, 3 stage II, 2 stage III) were diagnosed at our institution in the last 10 years. Five patients were treated with isoprinosine and the antiepileptic drug valproic acid. Three patients presented with myoclonic seizures refractory to valproic acid and the usual antiepileptic therapy. They received trihexyphenidyl with good results. We suggest the use of trihexyphenidyl in combination with isoprinosine in patients with subacute sclerosing panencephalitis with myoclonic seizures refractory to valproic acid.

Early onset bilateral calcifications and epilepsy.

Bilateral occipital calcifications associated with epilepsy and sometimes with celiac disease have been described previously. A boy with bilateral frontal and occipital diffuse calcifications accompanied by failure to thrive, nephrogenic diabetes insipidus, developmental delay and seizures, but without celiac disease is presented. Follow-up at 3 years of age disclosed neurodevelopmental delay, height and weight less than expected for age, and seizures controlled with carbamazepine. The uncommon association of these features and the early onset of symptoms is discussed. Although bilateral occipital calcifications share some clinical features with bilateral fronto-occipital calcifications, it is arguable whether the two are on a spectrum of a single disease or represent separate entities.