Mild Delay Research Articles

Complete versus anterior two-thirds corpus callosotomy in children: analysis of outcome

Object The goal of this study was to evaluate the efficacy of anterior versus complete sectioning of the corpus callosum in children suffering from medically refractory epilepsy. The authors report seizure outcome in patients who underwent anterior two-thirds or complete corpus callosotomy (CC) during the period 1995–2008 at St. Louis Children's Hospital. Methods The medical records of 27 children and adolescents with a minimum follow-up of 6 months were retrospectively evaluated with respect to seizure status, anticonvulsant outcomes, and subjective results. Preoperatively, patients suffered from a variety of seizure types that occurred daily, weekly, or episodically. The male/female ratio was 19:8, and patients ranged in age between 3 and 19 years (mean 9.93 years). Seizure outcome, parental assessment of daily function, and changes in the number of prescribed antiepileptic drugs were all assessed. Results Fifteen patients underwent an initial anterior two-thirds CC, and 12 underwent a complete CC. Of the 15 patients who underwent an anterior CC, 7 went on to receive a posterior CC. Seizure control was superior in children undergoing a complete CC (91%, Class I–III) versus an anterior two-thirds CC (75%, Class I–III). Seizure types most affected by CC included atonic, myoclonic, and absence. The number of postoperative antiepileptic drugs did not significantly change following CC in either the anterior only or complete groups. One patient experienced a transient disconnection syndrome that resolved within 4 weeks, and 4 patients experienced mild hemiparesis and speech delays that resolved with therapy. Three patients experienced surgical complications requiring a second operation. The overall daily function and attentiveness of the patients improved. Conclusions A complete CC should be considered as the initial procedure in lower-functioning children afflicted by absence, atonic, or myoclonic seizures. Severely affected higher-functioning children may also benefit from a complete CC, without clinically significant disconnection syndromes. A completion posterior CC may benefit patients in whom a prior anterior CC has failed.

Neurosurgical vascular malformations in children under 1 year of age

This study aims to analyze the clinical and radiological findings, timing and type of treatment, and outcome in children under 1 year of age that presented with neurosurgical vascular malformations. A retrospective review of 23 children under 1 year of age with neurosurgical vascular malformations was performed at a single institution between 1999 and 2009. The lesions found in this age group were: 10 vein of Galen aneurysmal malformations (VGAMs), 5 arteriovenous malformations (AVM), 2 pial arteriovenous fistulas (AVF; 1 in the brain and 1 in the spinal cord), 2 cavernous malformations, 2 dural sinus malformations (DSMs) in the posterior fossa with negative angiography which after surgery turned out to be embryonal malformations of dural sinuses, 1 sacular aneurysm, and 1 dural arteriovenous fistula (DAVF) that drained toward the vein of Galen. Of the 10 patients with VGAM, 8 presented choroidal type and 2 mural type. Two patients with choroidal VGAM were born in dramatically severe clinical condition; therefore, we decided to withhold aggressive treatment, and they died within 48 h after birth. The other eight patients with choroidal VGAM received endovascular treatment between 1 and 3 staged embolizations. In four of them, total occlusion was achieved and subtotal and partial in the others. One patient had complications and evolved with severe developmental delay. Another patient with partial occlusion died, and another patient with previous developmental delay stopped treatment because of parental decision making. Five patients evolved with normal development and one with mild delay. Only one patient required shunt. Hydrocephalus was solved after endovascular treatment in the rest of the patients. Regarding the five AVMs, four were treated with microsurgical approach achieving total resection of the lesion and normal developmental milestones except for one patient with brainstem AVM that was admitted with quadriparesis and coma. In the patient with basal ganglia AVM, the lesion spontaneously disappeared. From the two pial AVFs, the frontal one was microsurgically treated and the spinal one received endovascular session achieving 50% of lesion occlusion for which further treatment is needed. The two cavernous malformations were operated achieving total resection with normal development. The two children with DSM received surgical resection without complications and normal development. The rare case of sacular aneurysm at this age was occluded at the time of diagnostic procedure due to the bad clinical condition of the patient and the hematoma was removed immediately in the operating room. The only case of DAVF died of respiratory intercurrence after three sessions of endovascular treatment. In this neonatal age group (first year of life), we can find the whole range of neurosurgical vascular pathology: VGAM, AVM, cavernous malformation, DSM, pial AVF, DAVF, and sacular aneurysm. VGAM is the most frequent vascular malformation during the first year of age. The early treatment of vascular malformations prevents its adverse effects on a developing brain. A multidisciplinary team composed by endovascular and surgical specialists is necessary to discuss and treat each case.

Benign hereditary chorea: Clinical and neuroimaging features in an Italian family

Benign hereditary chorea is an autosomal dominant disorder characterized by early onset nonprogressive chorea, caused by mutations of the thyroid transcription factor-1 (TITF-1) gene. Clinical heterogeneity has been reported and thyroid and respiratory abnormalities may be present. We describe 3 patients of an Italian family carrying the S145X mutation in the TITF-1 gene with mild motor delay, childhood onset dyskinesias, and subtle cognitive impairment. A child in the third generation presented with congenital hypothyroidism and neonatal respiratory distress. Imaging studies in 2 patients showed mild ventricular enlargement and empty sella at magnetic resonance imaging and hypometabolism of basal ganglia and cortex at 18-Fluoro-2-deoxy-glucose positron emission tomography.

Maximum length sequence brainstem auditory evoked response in low-risk late preterm babies

Objectives. Recent research indicates that there is delayed development in the more central part of the auditory brainstem in very preterm babies. We aimed to study whether this is also the case for late preterm babies.Methods. The maximum length sequence brainstem auditory evoked response (MLS BAER) was used to study functional status of the auditory brainstem. Babies born at 33–36 week gestation and without any major perinatal complications were recruited. MLS BAER was recorded and analyzed at term age.Results. No significant correlation was found between most MLS BAER variables and physiological factors (gender, postconceptional age, bodyweight, and head circumference obtained at time of testing). Wave latencies and amplitudes, and I–V and I–III intervals in the preterm babies were essentially similar to those in the term controls at all click rates. However, III–V interval increased significantly at 227–910/s clicks (p < 0.05–0.01). All latencies, amplitudes and intervals correlated significantly with click rates (all p < 0.001). No differences were found in the slopes of MLS BAER variables–rate functions between the later preterm babies and term controls.Conclusions. Babies born at 33–36 weeks gestation without major complications had an increased III–V interval at high-rate stimulation. This suggests that late preterm babies have a mild delay in neural conduction in the more central part of the auditory brainstem.

Concurrent validity of the parent‐completed Ages and Stages Questionnaires, 2nd Ed. with the Bayley Scales of Infant Development II in a low‐risk sample

Abstract Background This study assessed the concurrent validity of the Ages and Stages Questionnaire (ASQ) compared with Bayley Scales of Infant Development II (BSID II) amongst children aged 24 months. Methods Data were collected from 53 infants and mothers who participated in the New York State Angler Cohort Child Development Study. Parents completed the 24-month ASQ to assess communication, personal-social, problem-solving ability, and fine and gross motor control. The BSID II was administered by a clinical psychologist at the 24-month home visit for cognitive and psychomotor assessment. The ASQ was scored using age-specific norms of <2 SDs below any domain mean to define failure. A BSID II score of <85 indicated mild or severe delay, while a score of <70 suggested a severe delay. Results Scores on the ASQ communication and personal-social domains were moderately correlated with the BSID II Mental Scale (R= 0.52, P < 0.001; R= 0.45, P < 0.01) and ASQ gross motor with the BSID II Motor Scale (R= 0.46, P < 0.01), whereas ASQ problem-solving and fine motor domains were not significantly correlated with BSID II scores. The ASQ had a sensitivity of 100% and specificity of 87% at 24 months (n= 40) for severely delayed status. Conclusions Results suggest the ASQs provide a simple, valid, and cost-effective method for clinicians and field-based researchers to reduce the number of standardized assessments required to identify developmentally delayed infants at age 24 months. Future studies should further assess the validity of the ASQs in larger, more diverse populations of infants.

Head bobbing due to succinic semialdehyde dehydrogenase deficiency

A 9-month-old boy had a short history of “yes-yes” head bobbing (video on the Neurology ® Web site at www.neurology.org). Mild global delay prompted investigation. Imaging (figure, A–C), biochemical, and molecular findings (table e-1) were consistent with succinic semialdehyde dehydrogenase …

The use of esophageal transit and gastric emptying studies in the evaluation of patients undergoing laparoscopic fundoplication

Preservation of esophageal and gastric function is a hallmark principle in ensuring optimal surgical outcomes after gastric fundoplication. In this study, we evaluated the impact of fundoplication on esophageal transit and gastric emptying using scintigraphy studies and related these functional findings to symptomatic outcomes. A total of 106 consecutive patients (37 women, 69 men) with both preoperative and 6-month postoperative nuclear scintigraphy studies undergoing partial (Toupet) fundoplication at a single institution were analyzed. Primary variables included alterations in esophageal transit and gastric emptying times after fundoplication (1 = rapid; 2 = normal; 3 = mild delay; 4 = severe delay). Symptomatic variables included heartburn, regurgitation, dysphagia, pulmonary symptoms, and bloating. Mean age was 57.2 years. Symptomatic improvement was achieved in 91.5% of patients. Significant reduction of all symptoms (heartburn, regurgitation, pulmonary symptoms, and dysphagia) was noted after fundoplication, except gas bloating (4.7 vs. 20.8%). There were no significant differences in preoperative and postoperative esophageal transit (2.53 vs. 2.52) and gastric emptying (2.13 vs. 2.06) scores after fundoplication. Interestingly, 17% of esophageal transit times and 18% of gastric emptying times improved after fundoplication. However, worsening scores were seen in 16 and 12%, respectively. There was no significant postoperative dysphagia, even in patients with impaired transit times. Nuclear scintigraphic assessment of esophageal transit and gastric emptying are valuable, user-friendly tools to identify and avoid functional motility problems in the setting of fundoplication. These studies seem to be a reasonable alternative to manometry in assessing esophageal function before surgery in this setting. Postoperative symptoms may be related to objective changes in esophageal transit or gastric emptying. The causes may be iatrogenic in nature or related to vagal denervation with associated changes in esophagogastric compliance. Awareness of these physiologic changes may prompt further technical precautions at the time of surgery to avoid vagal injury and also may facilitate postoperative medical management.

Delayed Recognition of Profound Hearing Loss in a 7-Year-Old Girl With a Neurological Condition

Kelly is a 7-year-old girl with a complex medical history including asthma, mild spastic diplegia, and seizure disorder that is controlled with carbamazepine. She had a significant receptive and expressive language impairment and milder delays in gross and fine motor skills. Kelly is currently repeating first grade in a self-contained classroom; she receives speech, occupational, and physical therapy. At the 7-year-old well child visit, her mother is worried about Kelly's poor progress in school, and she expresses concern about her daughter's hearing. Her pediatrician observes that Kelly is withdrawn, uses minimal language, and is fearful of the examination. Kelly was born full-term by Cesarean section because of placental abruption. She was in the neonatal intensive care nursery for 2 weeks with metabolic acidosis because of acute tubular necrosis. One day after arriving home, she had a cardiopulmonary arrest followed by emergency open-heart surgery for critical pulmonary hypertension. Her postoperative course was significant for renal failure, extracorporal membrane oxygenation, ventilator dependency, tracheostomy, and gastrostomy. By 3 years of age her medical condition stabilized, and the tracheostomy and gastrostomy tubes were removed. A review of Kelly's previous audiological tests revealed a failed otoacoustic emission test at 5 months. An auditory brain stem response test at 8 months recorded normal hearing in the right ear. At 4 years, behavioral audiometry was attempted but not completed because Kelly cried throughout the session. At 5 years, testing with ear inserts showed normal hearing bilaterally. Because of the concerns raised by Kelly's mother at the pediatric visit, she was referred to audiology for a reevaluation. Testing at this time revealed moderate to profound sensorineural hearing loss in both the ears, which was confirmed on subsequent examinations. Kelly was promptly fitted for hearing aids. Her individual education plan was changed to reflect the diagnosis of hearing impairment, and hearing services were implemented in the classroom. On a recent follow-up visit, Kelly was talkative, engaging, and cheerful.

Functional specialization of cellulose synthase genes of prokaryotic origin in chordate larvaceans

Extracellular matrices play important, but poorly investigated, roles in morphogenesis. Extracellular cellulose is central to regulation of pattern formation in plants, but among metazoans only tunicates are capable of cellulose biosynthesis. Cellulose synthase (CesA) gene products are present in filter-feeding structures of all tunicates and also regulate metamorphosis in the ascidian Ciona. Ciona CesA is proposed to have been acquired by lateral gene transfer from a prokaryote. We identified two CesA genes in the sister-class larvacean Oikopleura dioica. Each has a mosaic structure of a glycoslyltransferase 2 domain upstream of a glycosyl hydrolase family 6 cellulase-like domain, a signature thus far unique to tunicates. Spatial-temporal expression analysis revealed that Od-CesA1 produces long cellulose fibrils along the larval tail, whereas Od-CesA2 is responsible for the cellulose scaffold of the post-metamorphic filter-feeding house. Knockdown of Od-CesA1 inhibited cellulose production in the extracellular matrix of the larval tail. Notochord cells either failed to align or were misaligned, the tail did not elongate properly and tailbud embryos also exhibited a failure to hatch. Knockdown of Od-CesA2 did not elicit any of these phenotypes and instead caused a mild delay in pre-house formation. Phylogenetic analyses including Od-CesAs indicate that a single lateral gene transfer event from a prokaryote at the base of the lineage conferred biosynthetic capacity in all tunicates. Ascidians possess one CesA gene, whereas duplicated larvacean genes have evolved distinct temporal and functional specializations. Extracellular cellulose microfibrils produced by the pre-metamorphic Od-CesA1 duplicate have a role in notochord and tail morphogenesis.

Sequential neuroradiological and neurophysiological studies in a Japanese girl with merosin-deficient congenital muscular dystrophy

We describe the early manifestation and sequential assessment of the central and peripheral nervous system in a Japanese girl with merosin-deficient congenital muscular dystrophy. She showed severe hypotonia (‘‘floppy infant”) and suffered mild respiratory failure postnatally. Serum creatine kinase was elevated to 11,487 IU/L. The muscle biopsy showed dystrophic changes with negative expression of merosin (laminin α2), thereby confirming merosin-deficient congenital muscular dystrophy. Her motor milestones were severely delayed, but she could sit without support at the age of 3 years. After 3 years, her motor ability deteriorated and by the age of 5 years, she could not sit and control her neck. Magnetic resonance imaging (MRI) at 2 months of age revealed patterns that were appropriate for her age. At 1 year of age, the T2 weighted images showed diffuse high signal intensities throughout the centrum semiovale, and periventricular and subcortical white matter of the frontal and occipital lobes, while the U fibers, the corpus callosum and the internal capsule were spared. At the age of 7 years, these white matter abnormalities decreased. MR spectroscopy (MRS) revealed normal values of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr metabolite ratios as well as slightly increased myoinositol (mI)/Cr metabolite ratios. Neurophysiological motor nerve conduction velocity (MCV) and compound muscle action potential (CMAP) of the median nerve were in the normal range at the age of 2 months. After the child reached 1 year of age, the MCV and CMAP lagged behind those of healthy controlled children. The sensory nerve conduction velocity of the median nerve demonstrated a mild delay at the age of 15 months. It improved to normal range at the age of 6 years but decreased at 7 years of age . These sequential findings suggest not only that muscular degeneration and dysmyelination had occurred but also that various other factors, including demyelination and the vasogenic system, may influence the pathology of MDC1A.

Transient Axial Hypotonia and Alteration of Consciousness in an Infant With Chiari I Malformation

This is an 11-months-old girl, who presented to a pediatric neurologist with episodes of “becoming limp with eye deviation to the left and falling backwards while awake.” The first episode occurred 3 weeks before presentation as an isolated event, rapidly became frequent, occurring multiple times a day. The past medical history and development were normal except for mild gross motor delay, as the infant was not sitting unsupported at 10 months. The examination showed mild symmetric hypotonia with normal reflexes. Family history was unremarkable regarding neurological disorders. Magnetic resonance imaging (MRI) of the brain revealed Chiari I malformation with an abnormal T2 signal within the cervical cord, consistent with possible syringomyelia. Electroencephalogram (EEG) showed the presence of spikes in the left temporal region. During the EEG, a typical episode occurred, associated with diffuse delta activity. Because the nature of the events was unclear, and because of the potential need for surgical intervention, the infant was referred for further evaluation. Table 1 summarizes the diagnostic work-up in the hospital. Repeat MRI of the brain and spine, with and without gadolinium, confirmed Chiari I malformation, in which cerebellar tonsils extended approximately 1.5 cm below the foramen magnum. MRI of the cervical spine revealed focal expansion of the spinal cord at C2-C3 level with associated T2 signal changes (Fig 1). The degree of tonsillar ectopia with an abnormal T2 signal within the cervical spinal cord coupled with the developmental motor delay prompted a neurosurgical recommendation of decompressive craniotomy. Additionally, there was the clinical suspicion that the events of axial hypotonia may be caused by transient increases in intracranial pressure due to Chiari I malformation. Several target events were captured on video-EEG during the 7-day admission. Most of these events occurred while the infant was sitting. The infant would start responding poorly to the mother’s voice as well as ignoring the toys presented to her, then sway from side to side and become limp, followed by falling on her back with preserved bilateral finger and feet movements. The events lasted approximately 3 minutes, with a slow return to previous activities. There were no associated changes in respiration or cardiac patterns. Neurological examination showed that the infant was not responsive to verbal and visual stimulation, and there was proximal hypotonia

POST-OPERATIVE NEURODEVELOPMENTAL FINDINGS IN SYNDROMIC AND NON-SYNDROMIC CRANIOSYNOSTOSIS

Objective To evaluate the developmental situation of children that undergo operation because of syndromic and non-syndromic craniosynostosis. Materials & Methods In this prospective study, 24 children (4 to 16 months of age) who underwent neurosurgeryical intervention because of non-syndromic (79%) and syndromic (21%) craniosynostosis were recruited. For psychological evaluation, the Bayley Scales of Infant Development-Second Edition (BSID-II) was applied one month before and one year after surgical correction. The scale consists of three parts, Mental Developmental Index (MDI), Psychomotor Developmental Index (PDI), and Behavior Rating Scale. The MDI and PDI yield age-standard scores (100 ± SD). Results Mean baseline BSID-II scores revealed a mild delay in mental and motor scores (MDI: 84.3±2.1; PDI: 80.5±4.2) in non-syndromic craniosynostosis and a moderate delay in mental and motor scores (MDI: 70.3±3.1; PDI: 64.3±1.7) in syndromic craniosynostosis. Mean postoperative BSID-II score revealed improved motor scores (MDI: 91.3±0.1; PDI: 91.3±0.2) in non-syndromic craniosynostosis and mean postoperative BSID-II score revealed a mild delay in mental scores and no change in PDI. Among children with syndromic craniosynostosis, mean BSID-II score indicated mild baseline deficits in both mental and motor scores post operatively. Conclusion Mental development and prognosis was better in non-syndromic craniosynostosis comparing syndromic craniosynostosis. Surgery is effective in neurodevelopmental growth in non syndromic types of craniosynostosis but in syndromic type, remodeling surgery does not significantly affect neurodevelopmental outcome. Keywords : Craniosynostosis, BSID-II, Neurodevelopmental

Global developmental delay – globally helpful?

Identification of children with delay in acquisition of developmental milestones is a frequent reason for seeking a paediatric opinion. Around 17% of children referred to a community paediatric clinic, will be because of a developmental concern1 and is acknowledged as affecting 1–3% of children. 2 The role of the paediatrician is to seek to establish the aetiology and to help the child and family. Global developmental delay (GDD) is a term not used in the main index of either the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10)3 or the National Institute of Health CRISP thesaurus (now replaced by the RePORT Expenditures and Results query tool).4 In the former there is reference to specific developmental disorders, mixed or pervasive, and in the latter the term developmental disabilities is used. The term GDD, however, frequently appears in case notes, discharge letters, and journals. It is widely accepted that this term means significant delay in two or more areas of developmental performance: defined as gross/fine motor, speech/language, cognition, social/personal, and activities of daily living. Significant delay is defined as occurring when performance is two standard deviations below the mean on age appropriate, standardized norm reference tests. On developmental examination, however, we tend to separate gross motor and fine motor developmental domains since delay in one of these does not necessarily mean difficulties in the other (e.g. some neuromuscular disease). In addition, using this definition, children with autism would fulfil the criteria for GDD – but we don’t use this term when we see the triad of impairments associated with autism. I believe, therefore, that in practice we use the term GDD when the child has a motor delay and delays in at least two other areas of developmental performance. The majority of children with late acquisition of several developmental milestones will experience learning disability. As Newton and Wraith5 said, children with learning disability present in various ways and times, some in the newborn period, others in infancy and a few after school entry. It is, important however, that we convey our concerns to the parents in a realistic fashion at time of recognition, neither being too optimistic or pessimistic, but clarifying that delay in acquisition of developmental milestones usually means that the individual will have continuing difficulties with learning later in life.5,6 Do parents who are told their child had GDD appreciate what this means, or do they assume that development is slow but will get to its destination eventually? GDD is a term that parents may find unclear; it certainly is not a diagnosis and should not be used as a diagnostic term. A recent handbook of neurological investigations in children7 classifies the presenting neurological problem as the key to the investigative pathway and late attainment of all milestones is termed learning disability. What, therefore, would I recommend? Firstly, clinicians must continue to take a thorough history, examine the child, use standardized developmental assessments, seek therapists and teachers’ opinions, and describe the problem (e.g. late walking, late talking, etc.). Second, the cause of the delay must be investigated, bearing in mind that even mild delay may have a diagnostic cause.1 The vast majority of children with late development will go onto have learning disabilities of varying degree. There is a paucity of long-term data looking at outcomes of children with slow development under 5 years, but what is available suggests that early recognition of developmental delay appears to predict long-term learning problems. Better outcomes are found in children with more positive family support but further studies are needed.6 Clearly there is no consensus. It may be more helpful to use the ICD terms specific, mixed, or pervasive developmental disabilities, describing the developmental domains which are affected (e.g. walking, communication, etc.). Precision is preferable.

Differential Pathophysiological Mechanisms of Stroke Evolution between New Lesions and Lesion Growth: Perfusion-Weighted Imaging Study

Background: Stroke evolution frequently occurs during the first week after stroke. However, the association between the type of stroke evolution and baseline perfusion severity has not been investigated. Methods: We analyzed clinical and serial MRI data on patients with acute middle cerebral artery infarcts. Multimodal MRIs were acquired before treatment and on day 7. Time to peak (T_max) perfusion lesion maps were then generated, and changes in the day 7 diffusion-weighted imaging (DWI) were classified; new lesions were defined as new DWI lesions not contiguous with initial abnormalities, and infarct growth as enlargement of DWI lesions. Results: Among 74 patients (mean age 64.2 years), 51 received recanalization therapy. The day 7 DWI revealed the presence of new lesions in 39 cases (52.7%) and infarct growth (mean ± SD 20.0 ± 4.3 ml) in 52. No correlation was observed between new lesion and infarct growth (r = 0.029, p = 0.805). Most new lesions were multiple and small, located in cortical/superficial areas and within the mild perfusion delay (2 ≤ T_max < 4 s) regions, whereas infarct growth generally occurred within the severer perfusion delay regions. Multiple regression analysis revealed that large mild perfusion delay was independently associated with new lesions, whereas large initial DWI lesions and a severer perfusion delay (4 ≤ T_max < 8 s) were associated with infarct growth. In terms of treatment, endovascular therapy was associated with new lesions, whereas the degree of angiographic recanalization was inversely associated with infarct growth. Conclusions: The types of stroke evolution differed depending on the baseline hypoperfusion severity, and the mode and effect of recanalization therapy. A poor correlation was observed between new lesions and infarct growth.

Impact of Baseline Tissue Status (Diffusion-Weighted Imaging Lesion) Versus Perfusion Status (Severity of Hypoperfusion) on Hemorrhagic Transformation

The frequency of hemorrhagic transformation (HT) on gradient echo imaging and its impact on stroke outcomes continues to be debated. We investigated the factors associated with HTs and the influence of the HTs observed on gradient echo imaging on the early course after a stroke. We analyzed the data from a prospectively maintained registry of patients who were eligible for recanalization therapy. Serial diffusion-weighted imaging and perfusion-weighted imaging were performed, and HTs were assessed on follow-up gradient echo imaging. Tmax perfusion lesion maps were generated and hypoperfused regions were divided into severe (Tmax >or=8 seconds) delay and mild (Tmax >or=2 seconds but Tmax <8 seconds) delay. The factors associated with HTs, including the mode of recanalization therapy, pretreatment diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, and reperfusion indices, were evaluated. The early clinical outcome was assessed during the first 7 days of admission. A total of 184 patients were included in this study. HTs were noted in 73 (39.7%) patients. Multiple logistic regression analysis identified aggressive treatment (OR, 5.12; 95% CI, 1.73 to 15.18) and a large area of severe perfusion delay (OR for highest quartile of Tmax >8 seconds, 12.91; 95% CI, 3.69 to 45.17) as independent predictors of HTs. Neither risk factor profiles nor diffusion-weighted imaging lesion volumes were associated with HTs. There was a poor correlation between the radiological (HT types) and clinical (asymptomatic or symptomatic) categories of HTs. Even a parenchymal hematoma was not always associated with symptomatic worsening or affected the early clinical outcomes. The results of this study indicate that the perfusion status (severe perfusion delay) rather than the tissue status (diffusion-weighted imaging lesions) and aggressive treatment were independently associated with HTs. HT on gradient echo imaging was common but usually associated with severe hypoperfusion and not always associated with clinical deterioration.

Neurodevelopment of children born very preterm and free of severe disabilities: the Nord-Pas de Calais Epipage cohort study

To describe the development of very preterm children free of cerebral palsy or severe sensory impairment in the domains of gross and fine motor functions, language and sociability at a corrected age of 2 years; to identify factors associated with performances in each domain.A total of 347 children born in 1997 before 33 weeks of gestation, part of the EPIPAGE population-based cohort study, had their psychomotor development assessed with the Brunet-Lezine scale.The study population had a mean gestational age of 30.1 +/- 2.0 weeks. Lower developmental quotients (DQ) were observed in the study group compared to the reference sample (96 +/- 13 vs 104 +/- 8, p < 0.01). Fine motor function, language and sociability were all affected with a p value <0.01. Multivariate analysis showed that duration of intubation and parents' educational and occupational levels were the only variables significantly related to each developmental domain (p < 0.01).Children very preterm and free of severe disabilities had mild delays in multiple areas of development. The mechanisms by which neonatal factors played a role need further investigation. However socioeconomic status had a great impact on development and our results underline the need for improved support of socioeconomically disadvantaged parents after a preterm birth.

A Korean Family with the Muenke Syndrome

The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. The birth prevalence is approximately one in 10,000 live births, accounting for 8-10% of patients with coronal synostosis. Although MS is a relatively common diagnosis in patients with craniosynostosis syndromes, with autosomal dominant inheritance, there has been no report of MS, in an affected Korean family with typical cephalo-facial morphology that has been confirmed by molecular studies. Here, we report a familial case of MS in a female patient with a Pro250Arg mutation in exon 7 (IgII-IGIII linker domain) of the FGFR3 gene. This patient had mild midfacial hypoplasia, hypertelorism, downslanting palpebral fissures, a beak shaped nose, plagio-brachycephaly, and mild neurodevelopmental delay. The same mutation was confirmed in the patient's mother, two of the mother's sisters and the maternal grandfather. The severity of the cephalo-facial anomalies was variable among these family members.

Long time no see: the Type and Contre-type concept

Long time no see: the Type and Contre-type concept

Ring 14 chromosome presenting as early‐onset isolated partial epilepsy

We report four infants (two males, two females) with ring 14 chromosome presenting with early-onset partial epilepsy. The first seizure occurred between 3 and 6 months (3, 3, 4, and 6mo respectively). In all four cases, diagnosis was based on early focal seizures, rather than on psychomotor retardation or morphological features, which were not prominent at seizure onset. Moreover, despite the young age of the patients and the high frequency of seizures, neither epileptic spasms nor progression to 'epileptic encephalopathy', such as hypsarrhythmia, were observed. Epilepsy remained partial in these patients. At the most recent follow-up, all four children had slight or mild psychomotor delay, and two of them had moderate non-specific dysmorphic traits. Data from the literature about epilepsy in ring 14 chromosome syndrome were also reviewed. Ring 14 chromosome syndrome may be revealed by isolated, early-onset focal epilepsy suggestive of focal lesions with only mild mental retardation and morphological features at the time of diagnosis. The characteristics of these observations differ from classic ring 14 syndrome, and may enlarge this clinical spectrum. Many unanswered questions remain concerning phenotype-genotype correlation and identification of the potential genes and molecular mechanisms responsible for epilepsy in patients with ring 14 syndrome.

Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations

To determine the spectrum of clinical, neuropsychological, and neuroradiologic features in patients with autosomal recessive primary microcephaly (MCPH) due to ASPM gene mutations. ASPM was sequenced in 52 unrelated MCPH probands. In patients with ASPM mutations, we evaluated the clinical phenotype, cognition, behavior, brain MRI, and family. We found homozygous or compound heterozygous ASPM loss-of-function mutations in 11 (22%) probands and 5 siblings. The probands harbored 18 different mutations, of which 16 were new. Microcephaly was severe after 1 year of age in all 16 patients, although in 4 patients the occipital-frontal circumference (OFC) at birth was decreased by only 2 SD. The OFC Z score consistently decreased after birth. Late-onset seizures occurred in 3 patients and significant pyramidal tract involvement in 1 patient. Intellectual quotients ranged from borderline-normal to severe mental retardation. Mild motor delay was noted in 7/16 patients. Language development was delayed in all patients older than 3 years. Brain MRI (n = 12) showed a simplified gyral pattern in 9 patients and several malformations including ventricle enlargement (n = 7), partial corpus callosum agenesis (n = 3), mild cerebellar hypoplasia (n = 1), focal cortical dysplasia (n = 1), and unilateral polymicrogyria (n = 1). Non-neurologic abnormalities consisted of short stature (n = 1), idiopathic premature puberty (n = 1), and renal dysplasia (n = 1). We provide a detailed description of features associated with ASPM mutations. Borderline microcephaly at birth, borderline-normal intellectual efficiency, and brain malformations can occur in ASPM-related primary hereditary microcephaly.