Hemispheric language organization after congenital left brain lesions: A comparison between functional transcranial Doppler and functional MRI.

This study investigated whether functional transcranial Doppler ultrasound (fTCD) is a suitable tool for studying hemispheric lateralization of language in patients with pre-perinatal left hemisphere (LH) lesions and right hemiparesis. Eighteen left-hemisphere-damaged children and young adults and 18 healthy controls were assessed by fTCD and fMRI to evaluate hemispheric activation during two language tasks: a fTCD animation description task and a fMRI covert rhyme generation task. Lateralization indices (LIs), measured by the two methods, differed significantly between the two groups, for a clear LH dominance in healthy participants and a prevalent activation of right hemisphere in more than 80% of brain-damaged patients. Distribution of participants in terms of left, right, and bilateral lateralization was highly concordant between fTCD and fMRI values. Moreover, right hemisphere language dominance in patients with left hemispheric lesions was significantly associated with severity of cortical and subcortical damage in LH. This study suggests that fTCD is an easily applicable tool that might be a valid alternative to fMRI for large-scale studies of patients with congenital brain lesions.

Feasibility of a home-based computerized cognitive training for pediatric patients with congenital or acquired brain damage: An explorative study.

OBJECTIVES: Pediatric brain damage is associated with various cognitive deficits. Cognitive rehabilitation may prevent and reduce cognitive impairment. In recent years, home-based computerized cognitive training (CCT) has been introduced in clinical practice to increase treatment opportunities for patients (telerehabilitation). However, limited research has been conducted thus far on investigating the effects of remote CCT for the juvenile population in contexts other than English-speaking countries. The aim of the present study was to investigate the feasibility of a home-based CCT in a group of Italian adolescents with brain damage. A commercially available CCT (Lumosity) developed in the English language was used due to the lack of telerehabilitation programs in the Italian language that allow stimulation of multiple cognitive domains and, at the same time, remote automatic collection of data. Thus, this investigation provides information on the possibility of introducing CCT programs available in foreign languages in countries with limited investment in the telerehabilitation field. METHODS: 32 adolescents aged 11-16 with a diagnosis of congenital or acquired (either traumatic or non-traumatic) brain damage participated in the study. They received 40 training sessions (5 days/week for 8 weeks). Before starting the training program, they received face-to-face demonstration of training exercises and written instructions in their mother tongue. The feasibility of both training and study design and procedures was assessed through 9 criteria taken from extant literature. RESULTS: All 9 feasibility criteria were met. 31 out of the 32 participants demonstrated adherence to the training program. 94.2% of training sessions were completed in the recommended timeframe. No significant technical issue was found. CONCLUSIONS: Telerehabilitation seems to be a feasible practice for adolescents with brain damage. A training program developed in a foreign language can be used to counter the unavailability of programs in patients' mother tongue. TRIAL REGISTRATION: The trial is registered with the ISRCTN registry with study ID ISRCTN59250807.

Tratamiento rehabilitador en el paciente infantouvenil con daño cerebral adquirido / Rehabilitation treatment in child and youth patients with acquired brain injury

El daño cerebral es una de las causas más frecuentes de muerte y discapacidad en la población infantojuvenil. La mejoría en la atención a los pacientes en el momento agudo y la evolución de la asistencia sanitaria han supuesto un aumento de la supervivencia de estos pacientes y también de las secuelas. Secuelas físicas, cognitivo-conductuales u orgánicas son frecuentes, y las segundas son unas de las más frecuentes y más limitantes en estos pacientes. El daño cerebral afecta al paciente, pero involucra a toda la familia por la discapacidad que implica y por la dependencia que conlleva. El equipo es multidisciplinar, y el médico rehabilitador hace las funciones de coordinación. La familia debe recibir asistencia desde el primer día y es parte importante en la evolución adecuada de los pacientes. El tratamiento debe ser individualizado y adaptado para cada paciente, y suele durar entre 6 y 18 meses (AU)

Brain injury is one of the most frequent causes of death and disability in the child and adolescent. The improvement in patient care in the acute moment and the evolution of health care has meant and increase in the survival of these patients and also of the sequelae. Physical, cognitive-behavioral or organic symptoms are usually. The second is being one of the most frequent and most limiting in these patients. The brain injury affects the patient but involves the whole family because of the disability and the dependence it entails. The team is multidisciplinary and the rehabilitation physician performs the coordination functions. The family should receive assistance from the first day and are an important part in the proper evolution of patients. The treatment must be individualized and adapted for each patient and usually last between 6 and 18 months (AU)

Mutations of the thyroid hormone transporter MCT8 cause prenatal brain damage and persistent hypomyelination.

CONTEXT: Mutations in the MCT8 (SLC16A2) gene, encoding a specific thyroid hormone transporter, cause an X-linked disease with profound psychomotor retardation, neurological impairment, and abnormal serum thyroid hormone levels. The nature of the central nervous system damage is unknown. OBJECTIVE: The objective of the study was to define the neuropathology of the syndrome by analyzing brain tissue sections from MCT8-deficient subjects. DESIGN: We analyzed brain sections from a 30th gestational week male fetus and an 11-year-old boy and as controls, brain tissue from a 30th and 28th gestational week male and female fetuses, respectively, and a 10-year-old girl and a 12-year-old boy. METHODS: Staining with hematoxylin-eosin and immunostaining for myelin basic protein, 70-kDa neurofilament, parvalbumin, calbindin-D28k, and synaptophysin were performed. Thyroid hormone determinations and quantitative PCR for deiodinases were also performed. RESULTS: The MCT8-deficient fetus showed a delay in cortical and cerebellar development and myelination, loss of parvalbumin expression, abnormal calbindin-D28k content, impaired axonal maturation, and diminished biochemical differentiation of Purkinje cells. The 11-year-old boy showed altered cerebellar structure, deficient myelination, deficient synaptophysin and parvalbumin expression, and abnormal calbindin-D28k expression. The MCT8-deficient fetal cerebral cortex showed 50% reduction of thyroid hormones and increased type 2 deiodinase and decreased type 3 deiodinase mRNAs. CONCLUSIONS: The following conclusions were reached: 1) brain damage in MCT8 deficiency is diffuse, without evidence of focal lesions, and present from fetal stages despite apparent normality at birth; 2) deficient hypomyelination persists up to 11 years of age; and 3) the findings are compatible with the deficient action of thyroid hormones in the developing brain caused by impaired transport to the target neural cells.

Gestational iron deficiency differentially alters the structure and function of white and gray matter brain regions of developing rats.

Gestational iron deficiency (ID) has been associated with a wide variety of central nervous system (CNS) impairments in developing offspring. However, a focus on singular regions has impeded an understanding of the CNS-wide effects of this micronutrient deficiency. Because the developing brain requires iron during specific phases of growth in a region-specific manner, we hypothesized that maternal iron deprivation would lead to region-specific impairments in the CNS of offspring. Female rats were fed an iron control (Fe+) or iron-deficient (Fe-) diet containing 240 or 6 µg/g iron during gestation and lactation. The corpus callosum (CC), hippocampus, and cortex of the offspring were analyzed at postnatal day 21 (P21) and/or P40 using structural and functional measures. In the CC at P40, ID was associated with reduced peak amplitudes of compound action potentials specific to myelinated axons, in which diameters were reduced by ∼20% compared with Fe+ controls. In the hippocampus, ID was associated with a 25% reduction in basal dendritic length of pyramidal neurons at P21, whereas branching complexity was unaffected. We also identified a shift toward increased proximal branching of apical dendrites in ID without an effect on overall length compared with Fe+ controls. ID also affected cortical neurons, but unlike the hippocampus, both apical and basal dendrites displayed a uniform decrease in branching complexity, with no significant effect on overall length. These deficits culminated in significantly poorer performance of P40 Fe- offspring in the novel object recognition task. Collectively, these results demonstrate that non-anemic gestational ID has a significant and region-specific impact on neuronal development and may provide a framework for understanding and recognizing the presentation of clinical symptoms of ID.

[Neonatal cervical artery dissection secondary to birth trauma]. / Dissection artérielle cervicale néonatale secondaire à un traumatisme obstétrical.

Cervical artery dissection is rare in the neonatal period and is most often caused by birth injury during dystocic labor. The severity of this pathology is due to the possibility of serious neurological complications. We report a case of a male newborn who was born vaginally after shoulder dystocia. The extraction was difficult, resulting in a fracture of the right humerus. On the second day of life, the child presented generalized clonic convulsions. Computed tomography of the brain showed an ischemic stroke in the territory of the right middle cerebral artery, the territory of the right posterior cerebral artery, and the right lenticulostriate and capsular regions. Doppler ultrasonography and magnetic resonance angiography showed bilateral carotid artery thrombosis and dissection at the left common carotid artery and its two branches and the right vertebral artery. We discuss the mechanisms of this pathology and we emphasize preventive measures.

Atypical retinotopic organization of visual cortex in patients with central brain damage: congenital and adult onset.

It remains unclear to what extent retinotopic maps can undergo large-scale plasticity following damage to human visual cortex. The literature has predominately focused on retinotopic changes in patients with retinal pathologies or congenital brain malformations. Yet, damage to the adult visual cortex itself is common in cases such as stroke, tumor, or trauma. To address this issue, we used a unique database of fMRI vision maps in patients with adult-onset (n=25) and congenital (n=2) pathology of the visual cortex. We identified atypical retinotopic organization in three patients (two with adult-onset, and one with congenital pathology) consisting of an expanded ipsilateral field representation that was on average 3.2 times greater than healthy controls. The expanded representations were located at the vertical meridian borders between visual areas such as V1/V2. Additionally, two of the three patients had apparently an ectopic (topographically inconsistent) representation of the ipsilateral field within lateral occipital cortex that is normally associated with visual areas V3/V3A (and possibly other areas). Both adult-onset cases had direct damage to early visual cortex itself (rather than to the afferent drive only), resulting in a mostly nonfunctional hemisphere. The congenital case had severe cortical malformation of the visual cortex and was acallosal. Our results are consistent with a competitive model in which unilateral damage to visual cortex or disruption of the transcallosal connections removes interhemispheric suppression from retino-geniculate afferents in intact visual cortex that represent the vertical meridian and ipsilateral visual field.

[Prenatal cerebrovascular accidents diagnosed in the early infant stage: a series of 10 patients]. / Accidentes cerebrovasculares prenatales diagnosticados en la etapa de lactante: serie de 10 pacientes.

INTRODUCTION. A foetal or prenatal cerebrovascular accident (CVA) is defined as an ischaemic, thrombotic or arterial or venous haemorrhagic event that occurs between the 14th week of gestation and the onset of labour. PATIENTS AND METHODS. We report a retrospective study of a series of 10 patients suffering from a, presumably foetal, stroke that went unnoticed during the pregnancy and was diagnosed in the early infant stage. The symptoms and the age at which they were identified are highlighted. RESULTS. None of the 10 patients studied presented any relevant events in the mothers' medical history, but there were four threats of a preterm birth that were solved using the usual means and without the occurrence of any alterations that later affected the foetus. The studies that led to the diagnosis were carried out between the sixth and ninth months of life, and the reason for visiting was reported by the family as being a lower degree of mobility on one side of the body with respect to the other. Two patients presented thrombophilia. With a mean follow-up time of six years, all the patients have an associated infantile cerebral palsy, a third of them have epilepsy and 75% have learning difficulties or intellectual disability. CONCLUSIONS. When CVA are not detected in the prenatal period, it is important in primary care to look for and detect the warning signs of the psychomotor development of the infant at an early stage in order to begin a study of the case and to undertake rehabilitation as early as possible.

TITLE: Accidentes cerebrovasculares prenatales diagnosticados en la etapa de lactante: serie de 10 pacientes.Introduccion. El accidente cerebrovascular (ACV) fetal o prenatal se define como un suceso isquemico, trombotico o hemorragico arterial o venoso que acontece entre las 14 semanas de gestacion y el inicio del parto. Pacientes y metodos. Estudio retrospectivo de una serie de 10 pacientes afectos de un ictus, presumiblemente fetal, desapercibido durante el embarazo y diagnosticado en la etapa de lactante; se destacan cuales han sido los sintomas y la edad en que se han identificado. Resultados. De los 10 pacientes estudiados, ninguno presentaba antecedentes maternos relevantes, pero se detectaron cuatro amenazas de parto pretermino que se resolvieron con las medidas habituales y sin hallazgos de alteracion fetal posterior. Entre el segundo y tercer trimestre de vida es cuando se han realizado los estudios que han llevado al diagnostico, y se ha indicado por la familia una menor movilidad de un hemicuerpo respecto al contralateral como motivo de consulta. Dos pacientes presentaban una trombofilia. Con una media de seguimiento de seis años, todos asocian una paralisis cerebral infantil, la tercera parte una epilepsia y el 75% tiene dificultades de aprendizaje o discapacidad intelectual. Conclusion. Cuando los ACV no se detectan prenatalmente, es importante que en la atencion primaria se busquen y detecten los signos de alarma del desarrollo psicomotor del lactante de forma precoz para iniciar su estudio y procurar una rehabilitacion lo mas pronto posible.

Brain derived neurotrophic factor and oxidative stress index in pups with developmental hypothyroidism: neuroprotective effects of selenium.

Thyroid hormones (THs) are crucial for growth and development and particularly brain development. The present study was carried out to investigate the brain derived neurotrophic factor (BDNF) and Oxidative stress index (OSI) in the brain of pups born to dams with methimazole (MMI) induced hypothyroidism. Also, to elucidate the effectiveness of selenium (Se) in ameliorating the brain damaging effects induced by maternal hypothyroidism. Our results reveled that plasma free T3 (FT3), free T4 (FT4), growth hormone (GH) were significantly decreased while plasma thyroid stimulating hormone (TSH) was significantly increased in the pups. BDNF level significantly decreased while OSI significantly increased in both the hippocampus and cerebellum in pups born to hypothyroid dams. Se supplementation significantly alleviated the levels of these parameters. The biochemical modifications were confirmed histologically with the abnormal development of the hippocampus and cerebellum and partial reversal of these effects with Se supplementation. We concluded that reduced hippocampal and cerebellar BDNF levels and increment of oxidative stress during early development may contribute to the adverse neurodevelopmental effects of hypothyroidism during pregnancy. Also, Se is an important neuroprotective element that may be used as a dietary supplement against brain damage induced by hypothyroidism.

Severity of disability in patients with cerebral palsy secondary to symptomatic congenital cytomegalovirus encephalopathy.

PURPOSE: Cytomegalovirus (CMV) is a leading cause of congenital encephalopathy and cerebral palsy (CP). In this study we report the severity of disability in individuals who developed CP secondary to symptomatic congenital CMV encephalopathy. METHODS: The medical records of patients with CP secondary to symptomatic congenital CMV encephalopathy diagnosed from 1995 to 2011 were retrospectively reviewed. Gross Motor Functional Classification Scale (GMFCS) level, language function, and swallowing function were collected. RESULTS: Twenty-three patients were found. Of those 23 patients, 83% (19/23) were at a GMFCS level IV or V, 9% (2/23) each GMFCS level II or III and none (0%) at GMFCS I. Eighteen patients were non-verbal, 3 had minimal to moderate verbal skills and 2 had no verbal impairment. Eighteen patients also had severe dysphagia requiring gastrostomy tube (GT) feedings, and 5 ate orally. There was a strong correlation between the severity of GMFCS and having a gastrostomy tube (p< 0.0006) and GMFCS and verbal skills (p< 0.0023). CONCLUSION: This study shows that patients with CP secondary to symptomatic congenital cytomegalovirus encephalopathy have a very high risk of having severe physical and cognitive disabilities. This information can help healthcare providers and caregivers plan for the potential long-term medical, rehabilitation, and financial needs of this group of patients.

[Dichotic listening in Spanish-speaking children: validation of a set of dichotic lists of Spanish words and syllables]. / Test de escucha dicótica para niños hispanohablantes: validación de unas nuevas series de pares de palabras y de sílabas en castellano.

INTRODUCTION: Dichotic listening test can estimate hemispheric dominance for language. AIM: To study the usefulness of a new set of dichotic pairs of Spanish stimuli in middle childhood. SUBJECTS AND METHODS: The stratified control group comprised 40 healthy, right-handed children, aged 3.5- 7.5 years, of both sexes, with average ability at speaking Spanish. The clinical sample comprised 12 children with right spastic hemi-paretic cerebral palsy, average general intelligence and sentence repetition index over -2z. Each listening series is composed of 20 age-appropriate dichotic pairs: one syllable, word, or number; or trains of two or three syllables or numbers. Voice onset time, duration and stress of stimuli were balanced. Hemispheric dominance index (HDI) for language was calculated using a formula with the scores of stimuli from right or left ears. Statistical analysis evaluated the age-related accuracy and discriminant power of each HDI. RESULTS: In the non-forced attention paradigm, the range of HDI is 0-200. Values of HDI ≥ 112 indicate left hemisphere dominance for language, whereas values of HDI ≤ 88 indicate right hemisphere dominance. All 40 typical subjects showed left HDI for language, without influence of age and sex. In contrast, ten out of twelve (83%) right hemiparetic children had right HDI. CONCLUSIONS: The results show that this new set of dichotic pairs is useful in the initial assessment of cerebral dominance for language and valid for use in Spanish speaking children aged 3.5 years or more.

Qualitative brain MRI at term and cognitive outcomes at 9 years after very preterm birth.

OBJECTIVE: A prospective study was performed to assess the relationship between the appearance of cerebral MRI at term and the cognitive functioning at 9 years old in very preterm born infants. METHODS: Seventy-six very preterm born infants (birth weight <1500 g or gestational age ≤32 weeks) obtained cerebral MRI at term-equivalent period, which was assessed by using established composite scores for the white and gray matter; cognitive outcomes at 9 years old were assessed in 60 subjects by using Wechsler Intelligence Scale for Children, Third Edition. RESULTS: Mildly low scores on the different IQ indices (<85) were observed in 23.3% (verbal IQ), 41.7% (performance IQ), and 30.0% (full-scale IQ) of the cohort, whereas moderately low scores (<70) were noted in 3.3% (verbal IQ), 11.7% (performance IQ), and 11.7% (full-scale IQ); cerebral palsy was diagnosed in 10.0%, whereas special assistance at school was required in 56.7%. Abnormal white matter appearances predicted mildly low verbal, performance, and full-scale IQs; moderately low performance and full-scale IQs; cerebral palsy; and the requirement for special assistance at school. Abnormal white matter appearances predicted mild cognitive impairment even after the adjustment for known clinical risk factors. In contrast, abnormal gray matter appearances did not predict any of the outcome measures. CONCLUSIONS: In a cohort of very preterm born infants, abnormal white matter appearance on term MRI showed consistent associations with cognitive impairments at 9 years old, further supporting the benefit of obtaining term MRI for very preterm born infants.

Cerebral MRI abnormalities in a premature infant with later confirmed congenital central hypoventilation syndrome.

We present a premature infant with an inability to ventilate spontaneously during sleep periods. In addition, the patient showed general hypotonia. The child had a delayed passage of stool and increased anal muscle tone, indicating Hirschsprung's disease. The combination of these symptoms suggested congenital central hypoventilation syndrome, which was confirmed postmortem by DNA analysis showing a mutation in the PHOX2B gene. MRI of the brain showed damage to the white matter, including the internal capsula. This type of damage to the white matter has not been described before in a premature infant, who did not experience birth asphyxia.

Recurrence risk after a first remote symptomatic unprovoked seizure in childhood: a prospective study.

The aim of this study was to assess recurrence risk after a first remote symptomatic unprovoked seizure in childhood. All consecutive patients younger than 14 years with a first remote symptomatic unprovoked seizure who were seen at our hospital between 1994 and 2006 were included in the study and prospectively followed. Only two patients received antiepileptic treatment. Sixty-three children were included, with 35 males and 28 females. Mean age at first seizure was 4 years (SD 3y 5mo). Kaplan-Meier estimate of recurrence risk was 59% (95% confidence interval [CI] 47-71), 76% (95% CI 65-87), 85% (95% CI 76-94), and 87% (95% CI 78-96) at 6, 12, 18, and 24 months respectively. A total of 55 children out of 63 were affected by a static encephalopathy of pre- or perinatal origin. In this subgroup, recurrence risk at 12 and 24 months was 79% (95% CI 68-90) and 89% (95% CI 80-98). Univariable analysis using the Cox proportional hazards model showed that presence of global developmental delay/intellectual disability and Todd's paresis were associated with a significant increase in recurrence risk. In multivariable analysis, only Todd's paresis was significantly associated. Recurrence risk after a first remote symptomatic unprovoked seizure in childhood is much higher than what some previous studies suggests.

Timing of injury in the fetus and neonate.

PURPOSE OF REVIEW: The aim of this article is to assess evidence for the timing of brain injury associated with clinical encephalopathy in the fetus and newborn. RECENT FINDINGS: Older studies found strong epidemiological links between antenatal factors, including exposure to infection, and acute encephalopathy and later cerebral palsy. In contrast, recent cohort studies using early magnetic resonance imaging and spectroscopy, near-infrared spectroscopy and electroencephalogram monitoring suggest that the majority of brain injury in infants with evidence of encephalopathy occurs in the immediate perinatal period and conversely that it is relatively uncommon for chronic, antepartum injury to present with symptoms at birth. A key experimental study showed that mild infection can lead to long-lasting sensitization of the brain to subsequent mild hypoxia-ischemia. This provides a plausible mechanistic link between some antenatal complications and acute perinatal injury. Consistent with this, randomized controlled trials have demonstrated that therapeutic hypothermia can significantly improve outcome of neonatal encephalopathy at term. Electroencephalogram monitoring seems to be the most promising modality to identify infants who may benefit from potential neuroprotective treatments, but more research is needed to refine its use. SUMMARY: There is now strong evidence that brain injury commonly occurs in the immediate perinatal period, and so may be potentially treatable.

Congenital peri-sylvian syndrome presenting with intractable seizures.

We report a case of Congenital peri-sylvian syndrome with intractable seizures, hypotonia and feeding problems since birth. MRI brain helped in making an early diagnosis and counselling parents.

Apgar score predicts short-term outcome in infants born at 25 gestational weeks.

AIM: To identify early predictors of outcome in infants born at 25 gestational weeks. MATERIAL AND METHODS: Data from a regional perinatal database (time-period 1995-2001, total n = 108 000 births) were used. Apgar scores were available in 92 preterm infants, born at 25 + 0 to 25 + 6 gestational weeks, and analyzed in relation to short-term outcome (180-day survival with, or without, severe brain damage defined as intraventricular hemorrhage grade 3-4 or cystic periventricular leukomalacia). Based on multiple logistic regression analyses we constructed graphs of the estimated chance of survival. RESULTS: Apgar scores at 1, 5 and 10 min correlated with survival without severe brain damage (p = 0.02, 0.006 and 0.006, respectively). Survival without severe brain damage was higher in singleton than in multiple births (p = 0.03); there was no association with infant gender or mode of delivery. The strongest model for prediction of survival without severe brain damage was based on 5-min Apgar score and the Clinical Risk Index for Babies (CRIB), (p < 0.001). CONCLUSION: Apgar score predicts short-term outcome in extremely preterm infants at 25 gestational weeks. The precision for prediction of outcome increases when Apgar score is combined with CRIB.

Reorganisation of the somatosensory system after early brain damage.

OBJECTIVE: To examine the reorganisation of the somatosensory system after early brain lesions. METHODS: We studied 12 young patients with congenital hemiplegia. Causative lesions were brain malformations, periventricular injuries and cortico-subcortical lesions. We explored the somatosensory system using evoked potentials, fMRI during sensory stimulation and clinical assessment of sensory function. To correlate sensory and motor function, we also performed transcranial magnetic stimulation, fMRI of hand movement and assessment of motor function by means of Melbourne test. RESULTS: Eleven patients showed a perilesional reorganisation of primary somatosensory function, as expressed by short latency potentials following stimulation of the paretic hand; in a remaining patient, delayed latency responses (N27.1) were only elicited over the ipsilateral undamaged hemisphere. Five of the eleven patients with perilesional somatosensory representation of the affected hand showed contralesional shifting of motor function, thus exhibiting sensory-motor dissociation. Significant correlation was found between sensory deficit and fMRI activation during sensory stimulation. CONCLUSIONS: In subjects with early brain lesions, somato-sensory function is generally reorganised within the affected hemisphere. A contralesional shifting is uncommon and poorly efficient in function restoration. SIGNIFICANCE: This study confirms and further explores the difference in reorganisation capabilities of the motor and sensory system following early brain injury of different etiologies and timing.