Bone growth, modeling and remodeling in a supernumerary metatarsal bone associated with segmental gigantism in cutis marmorata telangiectatica congenita

Skeletal structure and processes of bone growth, modeling and remodeling were studied in a supernumerary metatarsal surgically removed from a 3-year-old boy affected by Cutis Marmorata Telangiectatica Congenita (CMTC), associated with hypertrophy of the right upper and lower limbs and postaxial hexadactylism of the homolateral hand and foot. No other anomalies were observed. The excess of periosteal growth, due to congenital anomaly, induced an abnormal development of both modeling and remodeling processes. In bone modeling, osteoblast activity on the periosteal surface was not paralleled by osteoclast resorption along the wall of the medullary canal, and this enormously increased the cortical thickness. In bone remodeling, osteoclastic resorption cavities were not refilled by secondary Haversian systems, thus inducing a severe bone loss. While the alteration of bone growth and modeling can be ascribed to the congenital disease, the unbalanced bone remodeling appears mainly to depend on mechanical disuse of the supernumerary metatarsal.     

Malformations of cortical development in children with congenital cytomegalovirus infection - A study of nine children with proven congenital cytomegalovirus infection

Congenital cytomegalovirus (CMV) infection is the most common vertically transmitted disease with the rate of the infection ranging from 0.2 to 2.4% in newborn infants. Congenital CMV infection causes multiorgan affection, but the most severe and permanent sequelae are those affecting central nervous system such as mental retardation, cerebral palsy, sensorineural hearing loss, chorioretinitis and seizures as a result of direct interference of the virus with neurogenesis. The time of acquiring infection is strongly connected to the level of child's disability. Infection in early pregnancy results in severe neurological sequelae, while later infection has less prominent signs. Radiological findings show connection between onset of infection and brain imaging, from lissencephaly, pachygyria, polymicrogyria, schizencephaly, calcification, cerebellar hypoplasia and/or hypoplasia/agenesis of corpus callosum as a result of an early infection, to white matter abnormalities including disturbed myelination as a result of a late infection. We present nine patients with proven congenital CMV infection and malformations of cortical development and their computed tomography/magnetic resonance (CT/MRI) findings along with clinical assessments. According to CT/MRI results we assume that two of our children with lissencephaly had an early onset of infection. The other seven with less severe cortical dysplasia in form of pachy/polymicrogyria were probably infected later Cerebellar hypoplasia and/or calcifications in our patients also confirm an early onset of infection. Developmental outcome in all of our children was poor: moderate to severe psychomotor retardation has been diagnosed in all children; five of them have developed cerebral palsy (four have bilateral spastic and one dyskinetic) and one is estimated to have minor motor dysfunction. Seven out of nine developed epilepsy, chorioretinitis was found in three of them and sensorineural deafness in two of them. All of our children, except one, were presented by symptomatic infection, yet only four of them were recognized at birth. Therefore, congenital CMV infection should be considered as one of the reasons for childhood disability more often.     

Unusual MRI findings of dural arteriovenous fistula: Isolated perfusion lesions mimicking TIA

ABSTRACT: BACKGROUND: The diagnosis of transient ischemic attack (TIA) based on clinical history and objective findings, even including multiparametric MRI, can be misleading. We report two patients who presented with TIA-like deficits with isolated perfusion lesions in corresponding areas but were finally diagnosed as transient neurological symptoms associated with dural arteriovenous fistula (dAVF). CASE PRESENTATION: Two patients presented with transient focal neurological symptoms lasting less than one hour. An isolated perfusion deficit with no diffusion change in the clinically relevant area was shown on brain MRI, indicating transient ischemia as the most plausible cause of neurological symptoms. However, cerebral angiography let to diagnosis of dAVF in both cases. Intracerebral hemorrhage occurred after the initial diagnosis of TIA in one patient, and the small area of perfusion abnormality accompanied by the enlarged cortical vein in the other case helped to identify the dAVF through the further investigation. The pattern of perfusion-weighted imaging in both cases revealed increase of mean transit time and relative cerebral blood volume denoting the venous congestion in a clinically corresponding area. CONCLUSION: Reported cases are uncommon clinical presentation of a dAVF, which can be misdiagnosed as TIA on clinical grounds. In rare cases, the isolated perfusion deficits could be attributable to venous congestion, despite the similar pattern of clinical presentation, such as with TIA.     

MRI Findings in 77 Children with Non-Syndromic Autistic Disorder

Background

The clinical relevance of MR scanning in children with autism is still an open question and must be considered in light of the evolution of this technology. MRI was judged to be of insufficient value to be included in the standard clinical evaluation of autism according to the guidelines of the American Academy of Neurology and Child Neurology Society in 2000 [1]. However, this statement was based on results obtained from small samples of patients and, more importantly, included mostly insufficient MRI sequences. Our main objective was to evaluate the prevalence of brain abnormalities in a large group of children with a non-syndromic autistic disorder (AD) using T1, T2 and FLAIR MRI sequences.

Methodology

MRI inspection of 77 children and adolescents with non-syndromic AD (mean age 7.4±3.6) was performed. All met the DSM-IV and ADI –R criteria for autism. Based on recommended clinical and biological screenings, we excluded patients with infectious, metabolic or genetic diseases, seizures or any other neurological symptoms. Identical MRI inspections of 77 children (mean age 7.0±4.2) without AD, developmental or neurological disorders were also performed. All MRIs were acquired with a 1.5-T Signa GE (3-D T1-FSPGR, T2, FLAIR coronal and axial sequences). Two neuroradiologists independently inspected cortical and sub-cortical regions. MRIs were reported to be normal, abnormal or uninterpretable.

Principal Findings

MRIs were judged as uninterpretable in 10% (8/77) of the cases. In 48% of the children (33/69 patients), abnormalities were reported. Three predominant abnormalities were observed, including white matter signal abnormalities (19/69), major dilated Virchow–Robin spaces (12/69) and temporal lobe abnormalities (20/69). In all, 52% of the MRIs were interpreted as normal (36/69 patients).

Conclusions

An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in non-syndromic autism. These results could contribute to further etiopathogenetic research into autism.     

West syndrome with periventricular leukomalacia: ten-year clinical study

The aim of the study was to evaluate magnetic resonance imaging (MRI) findings in infants with periventricular leukomalacia (PVL) and West syndrome (WS) and determine the neurodevelopmental outcome in children with West syndrome and PVL. Ultrasound and brain MRI were performed in 37 infants with recognized PVL. PVL was categorized according to De Vries, whereas West syndrome was categorized according to International League Against Epilepsy 1989. West syndrome in our patients developed during the first 2 years of life. The most common interictal abnormality was hypsarrhythmia. All, except two patients had delayed development and various degrees of mental retardation. The most characteristic neuroimaging findings were major reduction in cerebral cortical gray matter volume, reduction in the volume of brain myelin, and delayed myelination. These findings may explain the anatomical association between the West syndrome onset and PVL and intellectual and cognitive deficit in premature infants with PVL.     

Macrocephaly-cutis marmorata telangiectatica congenita: report of a patient with a translocation

Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous disorder. More than one half of the patients with CMTC have additional extra-cutaneous associated congenital anomalies. A subset of patients with CMTC have macrocephaly, the M-CMTC syndrome. This is a report on a patient with the M-CMTC syndrome and a de novo translocation t(2;17)(p11;p13). The etiology and pathology of the M-CMTC syndrome is unknown. Suggestions for the cause for M-CMTC include the occurrence of a new dominant mutation in a single gene, deletion of multiple contiguous genes at a level beyond the resolution of conventional karyotyping and chromosomal mosaicism. This patient did not have chromosomal mosaicism, however he had a translocation. It can be postulated that in the present patient the translocation breakpoints disrupted one or more genes entailing skin lesions but also other features: mental retardation, macrocephaly and facial dysmorphia.     

An additional manifestation in acrocallosal syndrome: temporal lobe hypoplasia

Acrocallosal Syndrome is a rare genetic disorder which is characterized by moderate to severe mental retardation, agenesis or hypoplasia of the corpus callosum and polydactyly of fingers and toes. The spectrum of this syndrome is very variable. Prominent forehead, broad nasal bridge, short nose and mandible, hypertelorism, epicanthic folds, large anterior fontanelle and tapered fingers, omphalocele and inguinal hernia are some other common findings in this syndrome. Twenty percent of the patients have associated brain abnormalities such as cerebral atrophy, hypothalamic dysfunction, small cerebrum, micropolygyria, hypoplasia of pons, hypoplasia of cerebellar hemispheres, hypoplasia of medulla oblongata, agenesis or hypoplasia of cerebellar vermis and corpus callosum abnormalities. Here we present a 10-month-old female infant with clinical and radiological findings indicative of acrocallosal syndrome. She was noted to have craniofacial abnormalities suggestive of acrocallosal syndrome, optic atrophy and polydactyly. MRI revealed cerebral atrophy, corpus callosum agenesis, dilated lateral ventricules and unilateral right temporal lobe hypoplasia, the latter not previously reported in the spectrum of this syndrome. Based on this observation we conclude the importance of screening brain abnormalities and present temporal lobe hypoplasia as a new additional anomaly in this syndrome.     

Alcohol and the fetus in the west of Scotland.

Forty children with the fetal alcohol syndrome were identified in the west of Scotland. All were growth retarded and had abnormal facial features, and all those who were tested were found to have neurological or developmental abnormalities. Two children died of associated physical defects. Most of the mothers were socially deprived, and all had drunk heavily while pregnant. Three women had subsequently died. These findings provide clear evidence that in the west of Scotland maternal alcohol abuse during pregnancy is a significant cause of morbidity and mortality in children.     

Neonatal White Matter Abnormalities an Important Predictor of Neurocognitive Outcome for Very Preterm Children

Background

Cerebral white matter abnormalities on term MRI are a strong predictor of motor disability in children born very preterm. However, their contribution to cognitive impairment is less certain.

Objective

Examine relationships between the presence and severity of cerebral white matter abnormalities on neonatal MRI and a range of neurocognitive outcomes assessed at ages 4 and 6 years.

Design/Methods

The study sample consisted of a regionally representative cohort of 104 very preterm (≤32 weeks gestation) infants born from 1998–2000 and a comparison group of 107 full-term infants. At term equivalent, all preterm infants underwent a structural MRI scan that was analyzed qualitatively for the presence and severity of cerebral white matter abnormalities, including cysts, signal abnormalities, loss of white matter volume, ventriculomegaly, and corpus callosal thinning/myelination. At corrected ages 4 and 6 years, all children underwent a comprehensive neurodevelopmental assessment that included measures of general intellectual ability, language development, and executive functioning.

Results

At 4 and 6 years, very preterm children without cerebral white matter abnormalities showed no apparent neurocognitive impairments relative to their full-term peers on any of the domain specific measures of intelligence, language, and executive functioning. In contrast, children born very preterm with mild and moderate-to-severe white matter abnormalities were characterized by performance impairments across all measures and time points, with more severe cerebral abnormalities being associated with increased risks of cognitive impairment. These associations persisted after adjustment for gender, neonatal medical risk factors, and family social risk.

Conclusions

Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on their term MRI appear to be spared many of the cognitive impairments commonly associated with preterm birth. Further follow-up will be important to assess whether this finding persists into the school years.     

The cerebro-morphological fingerprint of a progeroid syndrome: white matter changes correlate with neurological symptoms in xeroderma pigmentosum

Background

Xeroderma pigmentosum (XP) is a rare autosomal recessive progeroid syndrome. It has recently been shown that the underlying DNA repair defect plays a central role in the aging process. In addition to skin symptoms, various premature neurological abnormalities have been reported.

Methodology/Principal Findings

We present the clinical neurological phenotype in 14 XP patients (seven subtypes), in seven of these patients together with conventional and multiparametric advanced MRI data to assess the macrostructural and microstructural cerebral morphology in comparison to controls, including volumetric measurements, MR spectroscopy (¹H MRS), and diffusion tensor imaging (DTI). Clinical hallmarks were spinocerebellar ataxia, pyramidal tract signs, and mild cognitive deficits. DTI demonstrated significantly reduced WM directionality in all regions investigated, i.e. the thalamus, the corticospinal tracts and the dorsal corpus callosum. Single patients showed a marked relative hippocampal volume reduction, but the patients were not different from controls in the volumetric measurements of hippocampal and whole brain volumes at group level. However, ¹H MRS demonstrated that the hippocampal formation was metabolically altered.

Conclusions

The most prominent feature was the white matter affectation, as assessed by DTI, with volume and directionality reductions of the fiber projections involving both the craniocaudal fibers and the interhemispheric connections. These findings, although heterogeneous among the study sample, could be correlated with the clinico-neurological symptoms. The imaging findings support the position that myelin structures degrade prematurely in the brain of XP patients.     

Resection of small plexiform neurofibromas in neurofibromatosis type 1 children

BACKGROUND: Plexiform neurofibromas (PNF) are benign tumors of the peripheral nerve which mostly develop in patients with neurofibromatosis type 1 (NF1). Surgical interventions are usually not applied to children with small tumors. These are rather restricted to debulking of larger tumors in adults that cause clinical complications or aesthetic disfigurement. In most cases, a total resection of PNF is not possible due to the network-like growth of the tumors. PATIENTS AND METHODS: Early surgical intervention was carried out for 9 small PNFs in 7 NF1 children. Tumor resection was performed following the graphical delineation of the affected skin and according the MRI findings. RESULTS: Total resection was achieved for all 9 PNF without causing any neurological or organic deficit. Annual magnetic resonance tomography over a period of four years did not reveal any relapse of the tumors. CONCLUSIONS: Early surgical intervention for small superficial PNFs in NF1 children have various advantages and may especially be considered a strategy to prevent progression.     

缺血性脑卒中患者脑内微出血的发生及危险因素

目的:探讨脑内微出血(CMB)在缺血性脑卒中患者中的发生及相关危险因素。方法:连续选取住院的缺血性脑卒中患者250例,分析其磁共振成像(MRI)表现。根据有无CMB将患者分为CMB组(80例)及无CMB组(170例)。详细记录临床资料,观察CMB的个数、陈旧性腔隙性脑梗死的个数和脑白质改变(WMC)的严重程度。结果:单因素分析显示年龄、高血压病、既往脑梗死病史、脑白质改变、陈旧性腔隙性脑梗死及口服抗血小板聚集药物史与CMB的发生有关。Logistic回归分析显示高血压、既往有脑梗死病史及WMC分值为CMB的独立危险因素。结论:CMB与脑微血管病变之间有密切关系,高血压、既往有脑梗死病史及WMC分值为缺血性脑卒中患者发生CMB的独立危险因素。     

朗格罕细胞组织细胞增生症颅内垂体影像表现及相关临床表现

目的:探讨朗格罕细胞组织细胞增生症累及垂体的MR表现及相关临床表现。方法:搜集了6例确诊为朗格罕细胞组织细胞增生症并垂体表现异常的患儿,男5例,女1例,年龄2～11岁,平均(6±3)岁,对其影像及临床表现进行回顾性分析。结果:临床患儿主要以头面部包块,多饮、多尿等就诊。头颅MR平扫(T1WI)表现6例患儿神经垂体高信号全部消失,垂体柄增粗5例,垂体柄著征1例,垂体饱满1例,其中3例治疗后复查垂体及垂体柄均有变化。结论:神经垂体高信号消失,垂体柄增粗或著征为朗格罕细胞组织细胞增生症累及垂体的头颅MR表现。累及垂体者临床几乎都有多饮、多尿表现。目前,MRI是诊断朗格罕细胞组织细胞增生症累及垂体的唯一可靠的影像学检查方法,并对治疗后病情随访有重要作用。     

Thrombocytosis,circulating platelet aggregates,and neurological dysfunction.

In 12 patients whose neurological dysfunction was associated with thrombocytosis or evidence of abnormal platelet activation, or both, correction of the platelet disorder corresponded with reversal of the neurological symptoms. This suggests that platelet abnormalities may, in certain cases, produce several syndromes of neurological dysfunction, presumably as a result of obstruction of the cerebral microcirculation.     

视频脑电图和影像学检查对继发性癫痫患儿的诊断价值研究

目的:研究视频脑电图(V-EEG)和影像学检查对继发性癫痫患儿的诊断价值。方法:选取从2014年3月到2017年4月在我院接受诊治的癫痫患儿168例纳入本次研究。分别对所有患儿实施V-EEG和核磁共振成像(MRI)诊断,比较两种方式的诊断价值。结果:168例患儿中,V-EEG监测到154例有异常的脑电信号,其中120例有痫样放电,V-EEG显示痫样放电分布在左侧和右侧导联的比例较双侧导联明显更高(P0.05),MRI检测结果显示,140例患儿有颅内有关结构的病变亦或是发育异常,28例未发现异常。168例患儿中,发作类型为单纯部分型者72例,占比最高,为42.86%;主要病因中,颅内感染的发作类型以全身型为主,占11.31%。脑梗塞的发作类型以单纯部分型为主,占8.33%。颅内软化灶的发作类型以复杂部分型为主,占6.55%。颅内肿瘤的发作类型以单纯部分型为主,占6.55%。MRI定位主要在单侧,其中左侧占38.10%,右侧占29.76%;而经V-EEG监测显示异常放电154例,占91.67%,其中颅内感染和脑梗塞以及颅内肿瘤和颅内软化灶的阳性检出比例最高,分别为24.40%,13.10%,11.90%和10.71%。V-EEG诊断灵敏度和特异度均明显高于MRI(P0.05)。结论:V-EEG较MRI对继发性癫痫患儿的诊断价值更高,能够更加准确地提供诊断结果数据,值得在临床诊治过程中给予推广和应用。     

Brain Magnetic Resonance in the Diagnostic Evaluation of Mitochondrial Encephalopathies

Brain MR imaging techniques are important ancillary tests in the diagnosis of a suspected mitochondrial encephalopathy since they provide details on brain structural and metabolic abnormalities. This is particularly true in children where non-specific neurologic symptoms are common, biochemical findings can be marginal and genetic defects may be not discovered. MR imaging modalities include conventional, or structural, imaging (MRI) and functional, or ultrastructural, imaging (spectroscopy, MRS; diffusion, DWI-ADC; perfusion, DSCI––ASL). Among them MRI and MRS are the main tools for diagnosis and work up of MD, and this review will focus mainly on them. The MRI findings of MD are very heterogeneous, as they depend on the metabolic brain defects, age of the patient, stage and severity of the disease. No correlation has been found between genetic defects and neuroimaging picture; however, some relationships between MR findings and clinical phenotypes may be identified. Different combinations of MRI signal abnormalities are often encountered but the most common findings may be summarized into three main MR patterns: (i) non-specific; (ii) specific; (iii) leukodystrophic-like. Regarding the functional MR techniques, only proton MRS plays an important role in demonstrating an oxidative metabolism impairment in the brain since it can show the accumulation of lactate, present as a doublet peak at 1.33 ppm. Assessment of lactate should be always performed on brain tissue and on the ventricular cerebral spinal fluid. As for MRI, metabolic MRS abnormalities can be of different types, and two distinct patterns can be recognized: non-specific and specific. The specific metabolic profiles, although not frequent to find, are highly pathognomonic of MD. The un-specific metabolic profiles add value to structural images in allowing to define the lesion load and to monitor the response to therapy trials.     

Multiple sclerosis: the disease and its manifestations

Multiple sclerosis is an immune-mediated inflammatory demyelinating disease of the central nervous system clinically characterized by relapses and remissions of neurological disturbance. A typical relapse, exemplified by optic neuritis, increases in severity over a week or two and after approximately one month begins to remit. Resolution takes place over the course of two to three months. In the early stages, clinical recovery is virtually complete, though persistent abnormalities of conduction can usually be detected by evoked potential techniques and persistent structural abnormalities can be detected by magnetic resonance imaging (MRI). These techniques, together with cerebrospinal fluid examination for oligoclonal IgG, provide supporting evidence for the diagnosis which, in the absence of a specific test, nevertheless remains primarily clinical. The course of the disease is very variable, but after a number of years neurological deficit begins to accumulate after each relapse. In most patients, the relapsing and remitting phase of the disease is followed by a phase of continuous progression of disability. Cognitive disturbances can be detected in many patients even quite early in the course of the illness. Deficits in attention, memory and executive skills may be prominent and tend to become increasingly prominent as neurological deficit increases, although this is not always the case. There is some correlation between the extent of MRI abnormalities in the cerebral white matter and the severity of cognitive deficit. Depression and anxiety are commonly experienced but are poorly correlated to the lesion load seen on MRI. In contrast, the much rarer psychotic symptoms, euphoria and emotional lability are closely linked to the severity of white matter disease.     

Monitoring of subcortical and cortical somatosensory evoked potentials during carotid endarterectomy: comparison with stump pressure levels

Monitoring of multichannel somatosensory evoked potentials (SEPs) has been performed in 40 cases of carotid endarterectomy (CEA). SEPs were obtained after median nerve stimulation at wrist, recording from 2nd cervical and from the scalp parietal (ipsi- and contralateral) and central (contralateral) positions. The reduction of CBF due to clamping of the carotid artery provoked SEP abnormalities in 10 of the 40 cases. None of the 30 patients with unmodified SEPs developed post-surgical neurological sequelae.SEP alterations were characterized exclusively by amplitude decrements and latency increases of the cortical components, the subcortical ones being unaffected. In 5 of these patients, SEPs returned to normal values before the end of the intervention and no neurological deficit was observed on awakening. In the remaining 5 cases SEPs retained their abnormalities and patients developed post-surgery neurological sequelae (4 immediately, 1 the day after).SEP alterations affected parietal and central components to a similar extent; however, in a few cases cerebral blood flow deficits provoked by carotid clamping modified differently the central P22 and the parietal N20–P25 waves.Comparisons with stump (back) pressure in the carotid artery revealed a higher sensitivity of the SEP technique in detecting vascularization problems due to carotid clamping.The time course of the appearance of SEP abnormalities seems to discriminate alterations secondary to collateral revascularization from those determined by embolization.     

Early neurological complications of coronary artery bypass surgery.

A prospective study of 312 patients undergoing elective coronary artery bypass surgery was undertaken to determine the incidence, severity, and functional impact of postoperative neurological complications. Detailed evaluation of the patients showed that neurological complications after surgery were common, occurring in 191 of the 312 patients (61%). Although such a high proportion of the total developed detectable changes, serious neurological morbidity was rare. Neurological disorders resulted in death in only one patient (0.3%) and severe disability in only four (1.3%). Forty eight patients were mildly disabled during the early postoperative period, and the remaining 138 with neurological signs had no serious functional disability. The postoperative neurological disorders detected included one death from cerebral hypoxic damage. Prolonged depression of conscious level was observed in 10 patients (3%) and definite stroke in 15 (5%); 78 (25%) developed ophthalmological abnormalities and 123 (39%) primitive reflexes; postoperative psychosis was observed in four (1%); and 37 (12%) developed disorders of the peripheral nervous system. The incidence of serious neurological problems such as fatal cerebral damage, stroke, and brachial plexopathy is in accordance with experience elsewhere. Lesser abnormalities, whose detection required detailed neurological examination, were much commoner than expected from previous reports.     

Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A,not MYO5A

Griscelli syndrome (GS), a rare autosomal recessive disorder, is characterized by partial albinism, along with immunologic abnormalities or severe neurological impairment or both. Mutations in one of two different genes on chromosome 15q can cause the different subtypes of GS. Most patients with GS display the hemophagocytic syndrome and have mutations in RAB27A, which codes for a small GTPase. Two patients with neurological involvement have mutations in MYO5A, which codes for an actin-based molecular motor. The RAB27A and MYO5A gene products interact with each other and function in vesicle trafficking. We report the molecular basis of GS in a Muslim Arab kindred whose members have extremely variable neurological involvement, along with the hemophagocytic syndrome and immunologic abnormalities. The patients have normal MYO5A genes but exhibit a homozygous 67.5-kb deletion that eliminates RAB27A mRNA and immunocytofluorescence-detectable protein. We also describe the molecular organization of RAB27A and a multiplex polymerase chain reaction assay for the founder deletion in this kindred. Finally, we propose that all patients with GS have RAB27A mutations and immunologic abnormalities that sometimes result in secondary neurological involvement. The two patients described elsewhere who have MYO5A mutations and neurological complications but no immunologic defects may not have GS but instead may have Elejalde syndrome, a condition characterized by mild hypopigmentation and severe, primary neurological abnormalities.