RESUMEN
BACKGROUND: Perinatal stroke (PS) is the leading cause of hemiparetic cerebral palsy (CP). Involvement of the corticospinal tract on neonatal magnetic resonance imaging (MRI) is predictive of motor outcome in patients with hemiparetic CP. However, early MRI is not available in patients with delayed presentation of PS and prediction of hemiparesis severity remains a challenge. AIMS: To evaluate the volumes of the basal ganglia, amygdala, thalamus, and hippocampus following perinatal ischemic stroke in relation to hand motor function in children with a history of PS and to compare the volumes of subcortical structures in children with PS and in healthy controls. METHODS: Term born PS children with arterial ischemic stroke (AIS) (n = 16) and with periventricular venous infarction (PVI) (n = 18) were recruited from the Estonian Pediatric Stroke Database. MRI was accuired during childhood (4-18 years) and the volumes of the basal ganglia, thalamus, amygdala and hippocampus were calculated. The results of stroke patients were compared to the results of 42 age- and sex-matched healthy controls. Affected hand function was evaluated by Assisting Hand Assessment (AHA) and classified by the Manual Ability Classification System (MACS). RESULTS: Compared to the control group, children with AIS had smaller volumes of the ipsi- and contralesional thalami, ipsilesional globus pallidus, nucleus accumbens and hippocampus (p < 0.005). Affected hand function in children with AIS was correlated with smaller ipsilesional thalamus, putamen, globus pallidus, hippocampus, amygdala and contralesional amygdala (r > 0.5; p < 0.05) and larger volume of the contralesional putamen and hippocampus (r < - 0.5; p < 0.05). In children with PVI, size of the ipsilesional caudate nucleus, globus pallidus, thalamus (p ≤ 0.001) and hippocampus (p < 0.03) was smaller compared to controls. Smaller volume of the ipsi- and contralesional thalami and ipsilesional caudate nucleus was correlated with affected hand function (r > 0.55; p < 0.05) in children with PVI. CONCLUSIONS: Smaller volume of ipsilesional thalamus was associated with poor affected hand function regardless of the perinatal stroke subtype. The pattern of correlation between hand function and volume differences in the other subcortical structures varied between children with PVI and AIS. Evaluation of subcortical structures is important in predicting motor outcome following perinatal stroke.
Asunto(s)
Mano , Accidente Cerebrovascular , Núcleo Caudado , Niño , Femenino , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Embarazo , Accidente Cerebrovascular/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Extremidad SuperiorRESUMEN
Dravet syndrome is a severe epilepsy syndrome characterized by infantile onset of therapy-resistant, fever-sensitive seizures followed by cognitive decline. Mutations in SCN1A explain about 75% of cases with Dravet syndrome; 90% of these mutations arise de novo. We studied a cohort of nine Dravet-syndrome-affected individuals without an SCN1A mutation (these included some atypical cases with onset at up to 2 years of age) by using whole-exome sequencing in proband-parent trios. In two individuals, we identified a de novo loss-of-function mutation in CHD2 (encoding chromodomain helicase DNA binding protein 2). A third CHD2 mutation was identified in an epileptic proband of a second (stage 2) cohort. All three individuals with a CHD2 mutation had intellectual disability and fever-sensitive generalized seizures, as well as prominent myoclonic seizures starting in the second year of life or later. To explore the functional relevance of CHD2 haploinsufficiency in an in vivo model system, we knocked down chd2 in zebrafish by using targeted morpholino antisense oligomers. chd2-knockdown larvae exhibited altered locomotor activity, and the epileptic nature of this seizure-like behavior was confirmed by field-potential recordings that revealed epileptiform discharges similar to seizures in affected persons. Both altered locomotor activity and epileptiform discharges were absent in appropriate control larvae. Our study provides evidence that de novo loss-of-function mutations in CHD2 are a cause of epileptic encephalopathy with generalized seizures.
Asunto(s)
Proteínas de Unión al ADN/genética , Epilepsias Mioclónicas/genética , Animales , Niño , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/patología , Estudios de Cohortes , Epilepsias Mioclónicas/patología , Exoma , Femenino , Técnicas de Silenciamiento del Gen , Haploinsuficiencia , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Larva/genética , Masculino , Canal de Sodio Activado por Voltaje NAV1.1/genética , Fenotipo , Convulsiones Febriles/genética , Convulsiones Febriles/patología , Adulto Joven , Pez CebraRESUMEN
Cyclin-dependent kinase-like 5 (CDKL5) gene mutations have mainly been found in females with early infantile epileptic encephalopathy (EIEE), severe intellectual disability, and Rett-like features. To date, only 22 boys have been reported, presenting with far more severe phenotypic features. We report the first cases of CDKL5 gene-related EIEE in Estonia diagnosed using panels of epilepsy-associated genes and describe the phenotype-genotype correlations in three male and one female patient. One of the mutations, identified in a male patient, was a novel de novo hemizygous frameshift mutation (NM_003159.2:c.2225_2228del (p.Glu742Afs*41)) in exon 15 of CDKL5. All boys have a more severe phenotype than the female patient. In boys with early onset of seizures and poor development with absent or poor eye contact, CDKL5 gene-related EIEE can be suspected and epilepsy-associated genes should be analyzed for early etiological diagnosis. Early genetic diagnosis would be the cornerstone in personalized treatment in the future.
Asunto(s)
Epilepsia/genética , Mutación/genética , Proteínas Serina-Treonina Quinasas/genética , Espasmos Infantiles/genética , Adolescente , Preescolar , Estonia , Femenino , Estudios de Asociación Genética , Pruebas Genéticas , Humanos , Lactante , Masculino , FenotipoRESUMEN
Perinatal stroke is a leading cause of congenital hemiparesis and neurocognitive deficits in children. Dysfunctions in the large-scale resting-state functional networks may underlie cognitive and behavioral disability in these children. We studied resting-state functional connectivity in patients with perinatal stroke collected from the Estonian Pediatric Stroke Database. Neurodevelopment of children was assessed by the Pediatric Stroke Outcome Measurement and the Kaufman Assessment Battery. The study included 36 children (age range 7.6-17.9 years): 10 with periventricular venous infarction (PVI), 7 with arterial ischemic stroke (AIS), and 19 controls. There were no differences in severity of hemiparesis between the PVI and AIS groups. A significant increase in default mode network connectivity (FDR 0.1) and lower cognitive functions (p < 0.05) were found in children with AIS compared to the controls and the PVI group. The children with PVI had no significant differences in the resting-state networks compared to the controls and their cognitive functions were normal. Our findings demonstrate impairment in cognitive functions and neural network profile in hemiparetic children with AIS compared to children with PVI and controls. Changes in the resting-state networks found in children with AIS could possibly serve as the underlying derangements of cognitive brain functions in these children.
Asunto(s)
Encéfalo/fisiopatología , Cognición/fisiología , Disfunción Cognitiva/fisiopatología , Vías Nerviosas/fisiopatología , Accidente Cerebrovascular/fisiopatología , Mapeo Encefálico , Femenino , Humanos , Masculino , Red Nerviosa/fisiopatología , Pruebas Neuropsicológicas , Descanso , Accidente Cerebrovascular/complicacionesRESUMEN
Drug-induced acute pancreatitis is a rare condition in childhood, and information about the incidence of valproic acid-induced acute pancreatitis in the pediatric population is scarce. In this clinical case, we report a first documented pediatric case of valproic acid-induced pancreatitis in Estonia. A 15-year-old boy with juvenile myoclonic epilepsy developed acute pancreatitis after 2-month therapy with valproic acid. The symptoms of pancreatitis subsided within 1 week after the discontinuation of treatment with valproic acid. Acute pancreatitis should be suspected in any pediatric patient with gastrointestinal symptoms during valproate treatment.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia Mioclónica Juvenil/tratamiento farmacológico , Pancreatitis/inducido químicamente , Ácido Valproico/efectos adversos , Enfermedad Aguda , Adolescente , Anticonvulsivantes/efectos adversos , Estonia , Humanos , Masculino , Pancreatitis/diagnóstico , Pancreatitis/terapia , Ácido Valproico/uso terapéutico , Privación de TratamientoRESUMEN
Two cases of gelastic epilepsy in a 6-year-old girl with attacks of mirthful laughter and a 38-year-old male patient with episodes of laughter without any positive emotions are presented. Temporal lobe epilepsy was diagnosed in the first case and possible frontal lobe epilepsy in the second case. It is concluded that that this rare form of epilepsy can be difficult to diagnose and treat, and can clinically be accompanied by urinary incontinence.
Asunto(s)
Epilepsias Parciales/diagnóstico , Epilepsias Parciales/fisiopatología , Risa , Enfermedades Raras/diagnóstico , Enfermedades Raras/fisiopatología , Adulto , Niño , Electroencefalografía , Epilepsia del Lóbulo Frontal/diagnóstico , Epilepsia del Lóbulo Frontal/fisiopatología , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
AIMS: The aim of this study is to evaluate the value of early radiological investigations in predicting the long-term neurodevelopmental outcome of infants with inflicted traumatic brain injury (ITBI). METHODS: Clinical and radiological investigations of 24 infants with ITBI were performed during the acute phase of injury (1-3 days), and during the early (4 days up to 3 months) and late (>9 months) postinjury phases. The clinical outcome in survivors (n = 22) was based on the Rankin Disability Scale and the Glasgow Outcome Score. RESULTS: Five out of 24 infants (21%) had a poor neurodevelopmental outcome (death and severe disability), 17 infants (71%) had different developmental problems and 2 infants were normal at the mean age of 62 (54-70) (95% CI) months. A low initial Glasgow Coma Scale score of 8 or below [p < 0.05, OR 13.0 (1.3-133.3)], the development of brain oedema [p < 0.005, OR 13.0 (1.6-773)], focal changes in the basal ganglia during the acute phase [p < 0.01, OR 45 (2.1-937.3)], the development of new intracerebral focal changes early postinjury [p < 0.05, OR 24.1(1.0-559.1)], a decrease in white matter [p < 0.01, OR 33 (1.37-793.4)] and the development of severe atrophy before 3 months postinjury [p < 0.05, OR 24 (11.0-559.1)] were significantly correlated with a poor neurodevelopmental outcome. CONCLUSIONS: Early clinical and radiological findings in ITBI are of prognostic value for neurodevelopmental outcome.
Asunto(s)
Lesiones Encefálicas/diagnóstico , Maltrato a los Niños/diagnóstico , Evaluación de la Discapacidad , Lesiones Encefálicas/diagnóstico por imagen , Lesiones Encefálicas/mortalidad , Lesiones Encefálicas/rehabilitación , Niño , Maltrato a los Niños/mortalidad , Maltrato a los Niños/rehabilitación , Preescolar , Estonia/epidemiología , Femenino , Estudios de Seguimiento , Escala de Consecuencias de Glasgow , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Síndrome del Bebé Sacudido/diagnóstico , Síndrome del Bebé Sacudido/diagnóstico por imagen , Síndrome del Bebé Sacudido/mortalidad , Síndrome del Bebé Sacudido/rehabilitación , Tomografía Computarizada por Rayos XRESUMEN
Birth trauma, but not postnatal trauma, has been recognized as a cause of cerebral infarction in newborns. We report a case of cerebral infarction in a 27-day-old girl after a car accident. During the car accident, the child was properly restrained to the child's safety seat. The patient was admitted to the hospital for observation because of pronounced irritability. There were no focal neurological symptoms on admission. Twenty-eight hours after the accident, the child developed focal tonic-clonic seizures and mild right-sided hemiparesis. The seizures were successfully treated with phenobarbital at a dose of 30 mg per day. Computed tomography and magnetic resonance imagining performed on the second and third days after the accident, respectively, showed subdural hemorrhage in the occipital regions and cerebral ischemia in the left parieto-occipital region. Control imaging 10 days later showed signs of reperfusion. Persistent child irritability after head trauma is one of the indicating factors for performing an emergency computed tomography scan of the head.
Asunto(s)
Accidentes de Tránsito , Infarto Cerebral/etiología , Accidente Cerebrovascular/etiología , Anciano , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/diagnóstico por imagen , Urgencias Médicas , Femenino , Hematoma Subdural/diagnóstico , Hematoma Subdural/diagnóstico por imagen , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
This is a follow-up report of a girl, 5 years 4 months old, with classic symptoms of chronic paroxysmal hemicrania from the age of 2 years 3 months who had a complete response to indomethacin therapy. The patient suffered from frequent episodes of severe unilateral headaches for 1 year and 10 months before the diagnosis of chronic paroxysmal hemicrania was established. Indomethacin treatment lasted for 2 years and 6 months. During the first year of treatment, several doses of indomethacin were missed, which was followed by immediate return of hemicrania episodes and then quick resolution of symptoms after administration of indomethacin. After 2 years and 6 months of treatment, the parents missed the treatment for 1 week and the episodes did not recur. The treatment was discontinued. The patient was free from pain and off the medication 1 year later.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Indometacina/uso terapéutico , Hemicránea Paroxística/diagnóstico , Hemicránea Paroxística/tratamiento farmacológico , Antiinflamatorios no Esteroideos/administración & dosificación , Preescolar , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Cefalea/tratamiento farmacológico , Cefalea/fisiopatología , Humanos , Indometacina/administración & dosificación , Hemicránea Paroxística/fisiopatología , Resultado del TratamientoRESUMEN
The association between Down syndrome (DS), a genetic disorder resulting from trisomy of the 21st chromosome, and the autoantibodies of rheumatoid arthritis (RA) has been proposed but not unequivocally proven. The aim of this study was to determine whether adult patients with DS present higher levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies and/or rheumatoid factor (RF) than the general population. Our results showed that none of the 68 patients with DS had anti-CCP antibodies, whereas among 204 age- and sex-matched controls these autoantibodies were present in one person. However, DS patients presented a higher number of RF positive cases than controls (11.7% to 3.2% respectively; Fisher's exact test, pâ¯=â¯.027). The higher number of RF positive cases in the DS group without increase of anti-CCP antibodies may be indicative of immune disturbances in general rather than RA in these patients. Our study supports the view that RA does not occur with higher frequency in patients with DS than in the general population.
Asunto(s)
Síndrome de Down/sangre , Síndrome de Down/inmunología , Péptidos Cíclicos/inmunología , Factor Reumatoide/sangre , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Traumatic brain injury (TBI) is a major health problem in childhood. Estonia and other Baltic states have the highest trauma-related mortality in the European Union. There are no data on the incidence and causes of TBI for children in Estonia. The aim of this study was to estimate the incidence, structure and main causes of TBI in Tartu and Tartu County. METHODS: The study was carried out at Tartu University Hospital, between January 1, 2001, and December 31, 2005. For inclusion in the study the following criteria had to be fulfilled: age 0-14 years, documented brain trauma and neurological symptoms and residency in Tartu or Tartu County. Over the study period the inclusion criteria were fulfilled in 478 cases [272 boys (57%) and 206 girls (43%)]. RESULTS: The incidence of TBI in childhood in Tartu and Tartu County was 369:100,000 (405:100,000 for boys, 330:100,000 for girls). The incidence was highest among children from 0 to 4 years of age - 566:100,000. The main cause of TBI in all age groups was falling - 63.6%. According to severity, 82% of the cases were mild and 18% were moderate and severe. CONCLUSIONS: There is an urgent need for governmental prevention programs for TBI in children in Estonia.
Asunto(s)
Lesiones Encefálicas/epidemiología , Accidentes por Caídas/estadística & datos numéricos , Accidentes de Tránsito/estadística & datos numéricos , Adolescente , Distribución por Edad , Niño , Preescolar , Estonia/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Índice de Severidad de la Enfermedad , Distribución por SexoRESUMEN
We analyzed the relationship between magnetic resonance image findings in children with bilateral spastic cerebral palsy and its stages of severity in term and preterm children. Magnetic resonance image findings of 102 children (66 male and 36 female) with bilateral spastic cerebral palsy (median age, 2.5 years; range, 3 months to 15 years) were reevaluated. The study group consisted of children with confirmed perinatal asphyxia. Hypoxic-ischemic events were diagnosed in 64% of the children. Significant abnormalities relevant to cerebral palsy were evident on imaging in 85/102 (83%) children (in 77% of term and 93% of preterm children). Enlargement of the ventricles alone (48%) or accompanied by periventricular white-matter damage (25%) was the most frequent finding in term and preterm children, but was more highly expressed in preterm children (P < 0.05). White-matter damage was more often found in preterm children (P < 0.05). Enlargement of the lateral ventricles and periventricular leukomalacia may be attributable to ischemic damage to the neonatal brain. Significant correlations were found between magnetic resonance image findings and severity of cerebral palsy (P < 0.05). Detection of brain abnormalities in children with cerebral palsy may prove useful in prognoses as well as in medical consultations and management.
Asunto(s)
Encéfalo/patología , Parálisis Cerebral/complicaciones , Imagen por Resonancia Magnética/métodos , Espasticidad Muscular/etiología , Espasticidad Muscular/patología , Adolescente , Niño , Preescolar , Femenino , Lateralidad Funcional , Humanos , Lactante , Masculino , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: With an incidence up to 63 per 100,000 live births, perinatal stroke is an important cause of childhood epilepsy. The aim of the study was to find the prevalence of and predictive factors for epilepsy, and to describe the course of epilepsy in children with perinatal stroke with different vascular subtypes. METHODS: Patients were retrieved from the Estonian Paediatric Stroke Database with follow-up time at least 24 months. Patients were divided into 5 perinatal stroke syndromes: neonatal arterial ischemic stroke (AIS), neonatal hemorrhagic stroke, neonatal cerebral sinovenous thrombosis, presumed AIS, and presumed periventricular venous infarction. RESULTS: The final study group included 73 children with perinatal stroke (39 boys). With a median follow-up time of 8.6 years, epilepsy was diagnosed in 21/73 (29%) children, most of whom had AIS (17/21, 81%). The 18-year cumulative poststroke epilepsy risk according to the Kaplan-Meier estimator was 40.8% (95% confidence interval [CI] 20.7-55.9%). The median age at epilepsy diagnosis was 50 months (range 1 month to 18.4 years). Children with neonatal AIS had the highest risk of epilepsy, but children with presumed AIS more often had severe epilepsy syndromes. Cortical lesions (odds ratio [OR] 19.7, 95% CI 2.9-133), and involvement of thalamus (OR 9.8, 95% CI 1.8-53.5) and temporal lobe (OR 8.3, 95% CI 1.8-39.6) were independently associated with poststroke epilepsy. SIGNIFICANCE: The risk for poststroke epilepsy after perinatal stroke depends on the vascular subtype. Patients with perinatal AIS need close follow-up to detect epilepsy and start with antiepileptic treatment on time.
RESUMEN
The aim of this prospective epidemiological study was to establish the incidence rate of childhood epilepsy in Estonia, to describe the clinical spectrum and to identify etiology of childhood epilepsy. The overall incidence rate was 86.3/100 000. The incidence rate was the highest (141.9/100 000) in the age group from 5 to 9 years. Specific electroclinical syndromes were identified in 22.8% of cases. Structural or metabolic etiology was identified in 20.0% of cases, presumed genetic origin was identified in 33.9% of cases, and in 46.1% of cases the cause of epilepsy remained unknown. The incidence rate of childhood epilepsy in Estonia (86.3/100 000) is similar to the other European countries. In comparison with the results of the first epidemiological study of childhood epilepsy in Estonia (incidence rate 45/100 000; Beilmann et al), the incidence rate in this study is almost 2 times higher, what can be explained with better case collection and improved diagnostic modalities in Estonia.
Asunto(s)
Epilepsia/epidemiología , Adolescente , Distribución por Edad , Niño , Preescolar , Planificación en Salud Comunitaria , Variaciones en el Número de Copia de ADN , Electroencefalografía , Epilepsia/clasificación , Epilepsia/diagnóstico , Epilepsia/genética , Estonia/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: Liver-derived insulin-like growth factor-1 (IGF-1) contributes bone formation. Decreased IGF-1 levels are common in juvenile idiopathic arthritis (JIA), but whether IGF-1 is related to sex and differ during the pathogenic progress of JIA is unknown. OBJECTIVE: The aim of this study was to examine IGF-1 levels in boys and girls with newly diagnosed JIA, with established JIA and in controls. METHODS: The study group included 131 patients from the Estonian population-based prevalence JIA study. Blood samples were obtained from 27 boys and 38 girls with early JIA (≤1 month from the diagnosis), 29 boys and 36 girls with established JIA (mean disease duration 18 months), and from 47 age- and sex-matched controls. RESULTS: IGF-1 levels in boys were significantly decreased in early JIA compared to male controls, while IGF-1 levels in girls were comparable between JIA and controls. In early JIA, IGF-1 levels were 12-fold lower in boys relative to girls. In controls, IGF-1 levels correlated with both age and height, while these correlations were lost in boys with early JIA. CONCLUSION: We report a sex-dependent deficiency in serum IGF-1 in boys with early JIA, which argues for sex-related differences in biological mechanisms involved in the disease pathogenesis.
Asunto(s)
Artritis Juvenil/metabolismo , Proteínas Sanguíneas/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Grupos de Población , Factores Sexuales , Adolescente , Edad de Inicio , Artritis Juvenil/epidemiología , Niño , Estonia/epidemiología , Humanos , Masculino , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: Long-term follow-up data after different vascular types of ischemic perinatal stroke is sparse. Our aim was to study neurodevelopmental outcomes following neonatal and presumed perinatal ischemic middle cerebral artery territory stroke (arterial ischemic stroke, AIS) and periventricular venous infarction (PVI). METHODS: A prospective consecutive cohort of 40 term-born children with perinatal stroke (21 AIS, 19 PVI) was identified through the Estonian Paediatric Stroke Database. While 48% of the children with AIS were diagnosed during the neonatal period, all the children with PVI had presumed perinatal stroke. Outcomes based on the Paediatric Stroke Outcome Measure (PSOM) and Kaufman Assessment Battery for Children - Second Edition (K-ABC-II), in relation to extent and laterality of stroke, were defined. RESULTS: At a median age of 7 years 6 months (range 3.6-13y), there was a trend towards worse neurodevelopmental outcome in participants with AIS when compared to PVI (mean total PSOM scores 3.1 and 2.2, respectively; p = 0.06). Combined deficits of motor, language and cognitive/behavioural functions were significantly more common among children with AIS (90%) when compared to children with PVI (53%, p = 0.007). General cognitive ability (by K-ABC-II) was significantly lower in the AIS subgroup (mean 79.6; 95% CI 72.3-87.0), but children with PVI (91.6; 95% CI 85.5-97.8) also had poorer performance than the age-equivalent normative mean. Large extent of stroke was associated with poorer neurodevelopmental outcome and lower cognitive performance in children following AIS but not in PVI. CONCLUSION: In this national cohort, poor long-term neurodevelopmental outcome after perinatal ischemic stroke was seen irrespective of the vascular type or time of diagnosis of stroke. However, the spectrum of neurological deficits is different after perinatal AIS and PVI, with combined deficits more common among children following AIS.
Asunto(s)
Infarto Encefálico/complicaciones , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/etiología , Enfermedades del Recién Nacido , Accidente Cerebrovascular/complicaciones , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Estudios ProspectivosRESUMEN
OBJECTIVE: To characterize the neurologic phenotypes associated with COL4A1/2 mutations and to seek genotype-phenotype correlation. METHODS: We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with COL4A1/COL4A2 mutations. RESULTS: Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype. EEG typically showed focal epileptiform discharges in the context of other abnormalities, including generalized sharp waves or slowing. In 46.4% of new patients with focal seizures, porencephalic cysts on brain MRI colocalized with the area of the focal epileptiform discharges. In patients with porencephalic cysts, brain MRI frequently also showed extensive white matter abnormalities, consistent with the finding of diffuse cerebral disturbance on EEG. Notably, we also identified a subgroup of patients with epilepsy as their main clinical feature, in which brain MRI showed nonspecific findings, in particular periventricular leukoencephalopathy and ventricular asymmetry. Analysis of 15 pedigrees suggested a worsening of the severity of clinical phenotype in succeeding generations, particularly when maternally inherited. Mutations associated with epilepsy were spread across COL4A1 and a clear genotype-phenotype correlation did not emerge. CONCLUSION: COL4A1/COL4A2 mutations typically cause a severe neurologic condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. Early identification of patients carrying COL4A1/COL4A2 mutations may have important clinical consequences, while for research efforts, omission from large-scale epilepsy sequencing studies of individuals with abnormalities on brain MRI may generate misleading estimates of the genetic contribution to the epilepsies overall.
Asunto(s)
Colágeno Tipo IV/genética , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/patología , Adolescente , Adulto , Niño , Preescolar , Epilepsia/genética , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Mutación , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: There are not very many epidemiological studies on perinatal stroke, and many authors suggest that this may be an underdiagnosed condition. The aim of the study was to estimate the incidence of perinatal arterial ischemic and hemorrhagic stroke in Estonia, to study the first clinical signs and to identify possible differences in predisposing factors and outcome between acutely and retrospectively diagnosed cases of perinatal stroke. METHODS: A retro- and prospective study of acutely (within the first month) and retrospectively diagnosed ischemic and hemorrhagic cases of perinatal stroke was conducted in a children population born in the eastern and southern regions of Estonia during the years 1994 to 2003. Patients were identified from a pilot study, hospital records, and an inquiry of child neurologists and general practitioners. The diagnosis was confirmed in 38 (12 were diagnosed acutely and 26 retrospectively) cases by neuroradiology (MRI or CT). RESULTS: The incidence rate of perinatal stroke in Estonia is 63 per 100,000 live births. Main clinical findings in the neonatal period were seizures, abnormalities of muscular tone, and disturbed level of alertness. Previously identified risk factors occurred in 32% of cases. Children with early diagnosis had more often adverse events during pregnancy and delivery (P<0.05) and developed more severe stage of hemiparesis compared with children with late diagnosis (P<0.05). CONCLUSIONS: The incidence rate of 63 per 100,000 live birth is higher than previously reported. Detailed analysis of the first signs of perinatal stroke may improve the early diagnostics of perinatal stroke.
Asunto(s)
Isquemia Encefálica/epidemiología , Hemorragias Intracraneales/epidemiología , Complicaciones Cardiovasculares del Embarazo/epidemiología , Accidente Cerebrovascular/epidemiología , Isquemia Encefálica/diagnóstico , Causalidad , Estudios de Cohortes , Trastornos de la Conciencia/epidemiología , Diagnóstico Precoz , Estonia/epidemiología , Femenino , Humanos , Incidencia , Recién Nacido , Hemorragias Intracraneales/diagnóstico , Imagen por Resonancia Magnética , Masculino , Espasticidad Muscular/epidemiología , Paresia/epidemiología , Embarazo , Estudios Prospectivos , Estudios Retrospectivos , Convulsiones/epidemiología , Accidente Cerebrovascular/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
The authors present the case of an infant girl with severe generalized weakness, multiple bone fractures, and heart defect. She needed mechanical ventilation from birth. Radiographs showed mid-diaphyseal fractures of both humeri and of the right femur as well as generalized osteopenia. Electroneuromyography showed spontaneous fibrillations at rest with no active movements. Motor response to a stimulus could not be registered. A systolic heart murmur was detected, and echocardiography showed a large atrial septal defect and an additional membrane in the left atrium. DNA analysis confirmed the diagnosis of spinal muscular atrophy on the third day of life. Histology of the muscle showed both hypertrophic and atrophic fibers. Degenerating swollen neurons were found in the ventral horns of the spinal cord and also in the mesencephalic red nucleus, which has not been described before. Humeral bone showed only partly formed cortical bone. The spectrum of spinal muscular atrophy is very diverse, and atypical clinical findings do not always rule out 5q spinal muscular atrophy. The SMN1 gene should still be investigated.
Asunto(s)
Fracturas Óseas/complicaciones , Cardiopatías Congénitas/complicaciones , Atrofias Musculares Espinales de la Infancia/complicaciones , Femenino , Fracturas Óseas/patología , Cardiopatías Congénitas/patología , Humanos , Recién Nacido , Atrofias Musculares Espinales de la Infancia/patologíaRESUMEN
OBJECTIVE: To investigate the prevalence and causes of iron deficiency anemia in infants aged 9 to 12 months in Estonia. MATERIAL AND METHODS: Every second child aged 9-12 months was randomly selected from primary medical centers in seven counties from all over Estonia. A questionnaire concerning eating habits and lifestyle was sent to their parents. Sixty-five percent (n=195) of contacted families agreed to participate in the study. Mean corpuscular volume and hemoglobin, serum ferritin, and soluble transferrin receptor levels were measured in 171 infants. Anemia was defined when hemoglobin level was lower than 105 g/L, and iron deficiency when ferritin level and mean corpuscular volume were lower than 12 microg/L and 74 fL, respectively. RESULTS: The prevalence of iron deficiency was 14.0% and iron deficiency anemia 9.4%. Birthweight less than 3000 g was the main risk factor for iron deficiency (OR=9.4; P<0.0005). Infants fed with breast milk and solid food had lower ferritin concentration (18.5 microg/L, 95% CI 14.0-23.0) than infants fed with formula and solid food (32.8 microg/L, 95% CI 26.6-39) (P<0.005). CONCLUSION: Iron deficiency anemia is common among 9-12-month-old Estonian infants. The main risk factor for iron deficiency was birthweight less than 3000 g.