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OBJECTIVE: Recessive LAMC3 mutations are recognized to cause epilepsy with cortical malformations characterized by polymicrogyria and pachygyria. The objective of this study was to describe the clinical picture and epilepsy phenotype of four patients with a previously undescribed LAMC3 variant. METHODS: All epilepsy patients treated in Kuopio Epilepsy Center (located in Kuopio, Finland) are offered the possibility to participate in a scientific study investigating biomarkers in epilepsy (Epibiomarker study). We have collected a comprehensive database of the study population, and are currently re-evaluating our database regarding the patients with developmental and/or epileptic encephalopathy (DEE). If the etiology of epilepsy remains unknown in the clinical setting, we are performing whole exome sequencing to recognize the genetic causes. RESULTS: Among our study population of 323 DEE patients we recognized three patients with similar homozygous LAMC3 c.1866del (p.(Phe623Serfs*10)) frameshift variant and one patient with a compound heterozygous mutation where the same frameshift variant was combined with an intronic LAMC3 c.4231-12C>G variant on another allele. All these patients have severe epilepsy and either bilateral agyria-pachygyria or bilateral polymicrogyria in their clinical MRI scanning. Cortical malformations involve the occipital lobes in all our patients. Epilepsy phenotype is variable as two of our patients have DEE with epileptic spasms progressing to Lennox-Gastaut syndrome and intellectual disability. The other two patients have focal epilepsy without marked cognitive deficit. The four patients are unrelated. LAMC3 c.1866del p.(Phe623Serfs*10) frameshift variant is enriched in the Finnish population. SIGNIFICANCE: Only a few patients with epilepsy caused by LAMC3 homozygous or compound heterozygous mutations have been described in the literature. To our knowledge, the variants discovered in our patients have not previously been published. Clinical phenotype appears to be more varied than previously assumed and patients with a milder phenotype and normal cognition have probably remained unrecognized.
Assuntos
Epilepsia , Laminina , Malformações do Desenvolvimento Cortical , Humanos , Finlândia , Malformações do Desenvolvimento Cortical/genética , Malformações do Desenvolvimento Cortical/fisiopatologia , Malformações do Desenvolvimento Cortical/complicações , Feminino , Masculino , Epilepsia/genética , Epilepsia/fisiopatologia , Epilepsia/etiologia , Laminina/genética , Criança , Pré-Escolar , Fenótipo , Adolescente , MutaçãoRESUMO
Background and Objectives: Description of 15 patients with the same variant in DOK7 causing congenital myasthenic syndrome (CMS). Methods: Nine adult and 6 pediatric patients were studied with molecular genetic and clinical investigations. Results: All patients were identified with the c.1508dupC variant in DOK7, of whom 13 were homozygous and 2 patients compound heterozygous. Only 2 patients had limb girdle phenotype, while all adult patients also had ptosis, ophthalmoplegia, facial weakness, as well as inspiratory stridor. Pediatric patients had severe respiratory insufficiency and feeding difficulties at birth. Discussion: The disease severity in our patients varied extensively from ventilator or wheelchair dependence to mild facial weakness, ptosis, and ophthalmoparesis. Most of the patients had normal transmission in conventional 3 Hz stimulation electrophysiologic studies, making the diagnosis of CMS challenging. Our cohort of adult and pediatric patients expands the phenotype of DOK7 CMS and shows the importance of correct and early diagnosis.
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OBJECTIVES: The aim of this study was to evaluate associations between infant crying, holding and mother-infant interaction. METHODS: The study groups included 30 firstborn Finnish preterm infants (<1501 g or <32 weeks), and their 36 full-term controls. Caregiver's holding and infant's crying behavior was assessed using Baby Day Diary at 5 months of corrected age. The quality of mother-infant interaction was assessed using PC-ERA at 6 and 12 months of corrected age. RESULTS: The results showed that longer duration of holding in home environment was associated with better quality of mother-infant interaction at 6 and 12 months of corrected age in preterm infants. Preterm infants cried more often and were held more than full-term infants. The frequency of crying was associated with the duration of holding in preterm infants. Mother-infant interaction was comparable between the groups of preterm and full-term infants. CONCLUSIONS: Our results underline the importance of caregiver's physical closeness for the quality of the mother-infant interaction in preterm infants. Prematurity itself does not necessary affect the quality of mother-infants interaction in a non-risk population.
Assuntos
Cuidado do Lactente/psicologia , Recém-Nascido Prematuro/fisiologia , Relações Mãe-Filho , Mães/psicologia , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Choro/fisiologia , Choro/psicologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/psicologia , MasculinoRESUMO
OBJECTIVE: To evaluate the prevalence of various etiologies of epilepsies and epilepsy syndromes and to estimate cognitive function in cases of childhood-onset epilepsy. METHODS: A population-based retrospective registry study. We identified all medically treated children with epilepsy born in 1989-2007 in Finland's Kuopio University Hospital catchment area, combining data from the birth registry and the national registry of special-reimbursement medicines. We reevaluated the epilepsy diagnoses and syndromes and gathered data on etiologies and cognitive impairment. RESULTS: We identified 289 children with epilepsy. The annual incidence rate of epilepsies and epilepsy syndromes was 38 in 100,000, and the misdiagnosis rate was 3%. A specific etiology was identified in 65% of the cases, with a structural etiology accounting for 29% and a genetic or presumed genetic etiology for 32%. Most patients with unknown-etiology epilepsy had focal epilepsy and were of normal intelligence. Intellectual disability was detected in 35% of cases, and only 17% in this group had an unknown etiology for the epilepsy. Electroclinical syndromes (mainly West syndrome) were recognized in 35% of the patients. SIGNIFICANCE: Epilepsy is a complex disease that encompasses many etiologies and rare syndromes. The etiology and specific epilepsy syndrome are important determinants of the outcome and key factors in treatment selection. Etiological diagnosis can be achieved for the majority of children and syndromic diagnosis for only a third.
RESUMO
Event-related potentials were recorded from sleeping newborns to compare amplitudes and latencies of mismatch negativity (MMN) and late discriminative negativity (LDN) in active and quiet sleep stages. MMN and LDN were obtained in response to changes in semi-synthesized vowels from 20 healthy newborn infants. MMN and LDN responses were significant for both active and quiet sleep. The amplitude and latency of MMN or LDN did not differ between the sleep stages. Thus, in contrast to adult studies that show a significant drop in the MMN amplitude and an increase in the MMN latency as the sleep gets deeper, arousal stages do not seem to effect either MMN or LDN characteristics in newborns. These results suggest functional differences between infant and adult sleep.
Assuntos
Discriminação Psicológica/fisiologia , Potenciais Evocados/fisiologia , Fases do Sono/fisiologia , Estimulação Acústica/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Sono/fisiologiaRESUMO
The activity of the autonomic nervous system depends on sleep stage. The imbalance of the autonomic nervous system together with over-reactivity to stimuli has been suggested to be an etiologic factor for infantile colic. This study was designed to estimate the reactivity of the autonomic nervous system to a sleep-time stimulus in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep stages and in colic and control infants. Overnight sleep polygraphic recordings were performed for 12 colic and 14 control infants at the age of 8 weeks. Movements were detected by a static-charge-sensitive bed. Extent of heart rate variability (HRV) was measured in response to spontaneous sleep-related movements. HRV analysis was performed over 2-min segments during NREM and REM sleep before and after 5-36-s long movement periods. Total (0.04-1.0 Hz), low (0.04-0.15 Hz) and high frequency (0.15-1.0 Hz) HRV increased after the movement periods in light NREM sleep (p < 0.001). These changes were not observed in REM sleep. No differences were found between the colic and the control groups in HRV. The observed difference in the response of the HRV between sleep stages is likely to reflect the different characteristics of heart rate control in NREM and REM sleep, but our results do not suggest that colic infants would have abnormal autonomic reactivity to stimuli while asleep.
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Cólica/fisiopatologia , Frequência Cardíaca/fisiologia , Movimento/fisiologia , Sono/fisiologia , Feminino , Idade Gestacional , Humanos , Lactente , Masculino , Fases do Sono/fisiologia , Sono REM/fisiologiaRESUMO
BACKGROUND: This study was conducted to gain better understanding of the prolonged effects of pain and pain management on preterm infants' sleep. AIM: The hypothesis was that the sleep structure in very preterm infants is different after painful procedures with pain management (facilitated tucking by parents (FTP), oral glucose, and oxycodone) than without pain management (oral water as placebo). METHODS: A prospective randomized placebo-controlled cross-over trial design was used. Thirteen-hour polysomnographic recordings were conducted when the study infants (n=18) were at a post-conceptional age of 28-32 weeks. During the recordings, the standardized nursing care periods were carried out with different forms of pain management administered at 3-h intervals. Sleep structure was analyzed before and after the interventions. The main hypothesis was analyzed using mixed models. RESULTS: During the first post-intervention hour, the amount of rapid eye movement (REM) sleep decreased after all interventions regardless of pain management (p<0.001). However, the oxycodone treatment further reduced the amount of REM sleep to 48.0% (SD 14.9) compared to other interventions: oral glucose to 64.4% (SD 12.8), (p<0.001); placebo to 62.9% (SD 16.1), (p<0.001); and FTP to 61.6% (SD 1.9), (p=0.004). In addition, sleep onset comprised non-rapid eye movement (NREM) sleep more frequently after oxycodone (50%) compared to placebo (6%, p=0.006), oral glucose (11%, p=0.019) or FTP (17%, p=0.056). CONCLUSION: Pain management with oxycodone markedly altered the structure of the subsequent sleep period. This reduced amount of REM sleep may have consequences for brain development in preterm infants.
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Analgesia/métodos , Dor/tratamento farmacológico , Sono/fisiologia , Analgésicos Opioides/uso terapêutico , Estudos Cross-Over , Feminino , Glucose/uso terapêutico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Modelos Logísticos , Masculino , Oxicodona/uso terapêutico , Medição da Dor/métodos , Polissonografia , Estudos Prospectivos , Sono/efeitos dos fármacosRESUMO
OBJECTIVES: The purpose of this study was to compare the effectiveness of "facilitated tucking by parents" (FTP) in which a parent holds by her hands the infant in a side-lying flexed position offering support and skin contact, oral glucose, opioid (oxycodone), and placebo (oral water) in the context of heel stick and pharyngeal suctioning in very preterm infants. We hypothesized that nonpharmacologic methods equal the pharmacologic method and are superior to placebo in pain management. METHODS: A prospective randomized placebo-controlled crossover trial. The study patients (n=20) were born at a mean gestational age of 28(+1) weeks and were studied at postconceptional age of 28 to 32 weeks. Pain measurements with Premature Infant Pain Profile and Neonatal Infant Pain Scale covered the first 30 seconds after the beginning of the painful stimulus. RESULTS: Premature Infant Pain Profile scores were significantly lower with oral glucose (mean: 4.85+/-1.73, PAssuntos
Analgésicos Opioides/administração & dosagem
, Glucose/administração & dosagem
, Oxicodona/administração & dosagem
, Manejo da Dor
, Dor/psicologia
, Relações Pais-Filho
, Administração Oral
, Estudos Cross-Over
, Método Duplo-Cego
, Feminino
, Temperatura Alta/efeitos adversos
, Humanos
, Lactente
, Recém-Nascido
, Recém-Nascido Prematuro/fisiologia
, Recém-Nascido Prematuro/psicologia
, Masculino
, Dor/etiologia
, Medição da Dor/métodos
, Estudos Prospectivos
, Estudos Retrospectivos
, Sono/efeitos dos fármacos
, Sono/fisiologia
, Comportamento de Sucção/fisiologia
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AIM: To evaluate the association between infant fussing and crying and developmental outcome in very low birth weight (VLBW) infants. METHODS: Hundred and seventeen VLBW infants were followed up to 24 months of corrected age. The duration of fussing and crying and frequency of fuss/cry bouts were measured at term 6 weeks and 5 months of corrected age. Cognitive and motor development was assessed at 24 months of corrected age. RESULTS: The increased duration of combined fuss/cry at term associated with lower psychomotor developmental index (PDI), [regression coefficient (b)=-0.83, p=0.025]. Crying at term associated negatively with mental developmental index (MDI) (b=-0.91, p=0.040) and PDI (b=-1.10, p=0.015). The associations between fuss/cry and PDI, and crying and PDI persisted in multiple regression analysis (b=-0.89, p=0.030 and b=-1.23, p=0.018, respectively). Excessive fuss/cry (>or=180 min/day) at term associated with lower PDI (p=0.005) and at 6 weeks with lower MDI (p=0.024) and PDI (p=0.012). Increase in the frequency of fuss/cry bouts at 5 months associated with higher PDI in both simple (b=2.90, p=0.045) and in multiple regression analysis (b=3.60, p=0.019). CONCLUSIONS: In VLBW infants, longer duration of fussing and crying in very early infancy, but not at 5 months, is associated with less optimal development at 24 months of age.
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Choro , Comportamento do Lactente , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Prontuários Médicos , Transtornos Psicomotores/diagnóstico , Análise de RegressãoRESUMO
OBJECTIVES: The objective of this study was to assess crying behavior during infancy in very preterm infants with or without brain injury. METHODS: A total of 125 very low birth weight infants survived during January 2001 to July 2004 in Turku University Hospital, Finland. They were categorized according to the most pathologic brain finding either in ultrasound or MRI. Baby Day Diary was used to assess crying behavior at term, 6 weeks, and 5 months of corrected age. The behavior of a group of term control infants (n = 49) was assessed at 5 months. RESULTS: Severe brain injuries in very low birth weight infants did not affect the duration of fussing or crying. In very low birth weight infants, brain injuries did not affect the frequency of fussing or crying bouts or the development of circadian rhythm in crying behavior. At 5 months of corrected age, fussing bouts were more frequent in very low birth weight infants compared with term control infants (6.4 per day vs 4.5 per day), and very low birth weight infants were held more (169 minutes [97] vs 130 minutes [69], respectively). CONCLUSIONS: This prospective study using a validated cry diary showed that brain injuries that are related to prematurity do not have major effects on crying behavior or development of circadian rhythm. Prematurity does not increase the duration but increases the frequency of fussing and crying at 5 months of corrected age compared with term control infants. It also seems that prematurity and brain pathology may increase caregiving activity in the form of holding.
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Lesões Encefálicas/epidemiologia , Choro , Comportamento do Lactente , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Fatores Etários , Encefalopatias/diagnóstico por imagem , Ventrículos Cerebrais/patologia , Ritmo Circadiano , Humanos , Recém-Nascido , Leucomalácia Periventricular/diagnóstico por imagem , Leucomalácia Periventricular/epidemiologia , Imageamento por Ressonância Magnética , Estudos Prospectivos , UltrassonografiaRESUMO
OBJECTIVE: Parents' reports suggest that excessively crying or colicky infants sleep less compared with control subjects. The aim of this study was to determine the sleep-wake structure of excessively crying infants throughout a 24-hour cycle. METHODS: A 24-hour sleep polygraphy study was conducted at home for 24 excessively crying infants and 23 control subjects at the age of 6 weeks. In addition, parental diaries were kept for 4 days. RESULTS: In sleep polygraphy recordings, no major differences between study groups were observed in either the duration or the structure of the 24-hour sleep. In the diaries, the parents overestimated the amount of sleep in both study groups. The parents of the control infants overestimated the amount of sleep more than the parents of excessively crying infants (69.8 minutes [standard deviation: 79.3] compared with 27.1 minutes [standard deviation: 65.4], respectively). In excessively crying infants, the proportion of rapid eye movement sleep was higher during the 3-hour period from the beginning of the first long sleep in the evening and lower during the preceding 3-hour period compared with the control group. CONCLUSIONS: The results of this study suggest that diary-based studies are prone to be biased as the parents of the control infants are more likely to overestimate the amount of infant's sleep and, therefore, report more sleep than the parents of the crying infants. Although no differences in the total amount of sleep or proportions of sleep stages were observed, excessively crying infants may be characterized by a disturbance that affects rapid eye movement and non-rapid eye movement sleep stage proportion during evening hours.