Aberrant distribution of tyrosine hydroxylase and substance P in infants with brain-stem infarction

The distribution of tyrosine hydroxylase (TH) and substance P (SP) was examined in the brain-stem of 4 infants with respiratory abnormalities associated with remote brain-stem or cerebellar infarction utilizing immunohistochemical methods. TH-immunoreactive cells and SP-immunoreactive fibers were found in and around the area of the infarction in the tegmentum, in amounts and sites different from that seen in controls. The aberrant localization of SP and TH may represent an altered repair process associated with resolution of the infarction and may be related to abnormal respiratory control or sudden death.     

Long-term outcome for endoscopic third ventriculostomy alone or in combination with choroid plexus cauterization for congenital aqueductal stenosis in African infants

Object The authors have previously reported on the overall improved efficacy of endoscopic third ventriculostomy (ETV) combined with choroid plexus cauterization (CPC) for infants younger than 1 year of age. In the present study they specifically examined the long-term efficacy of ETV with or without CPC in 35 infants with congenital aqueduct stenosis treated at CURE Children's Hospital of Uganda during the years 2001-2006. Methods Infants with congenital aqueductal stenosis were treated during 2 distinct treatment epochs: all underwent ETV alone, and subsequently all underwent ETV-CPC. Prospectively collected data in the clinical database were reviewed for all infants with an age < 1 year who had been treated for hydrocephalus due to congenital aqueductal stenosis. Study exclusion criteria included: 1) a history or findings on imaging or at the time of ventriculoscopy that suggested a possible infectious cause of the hydrocephalus, including scarred choroid plexus; 2) an open aqueduct or an aqueduct obstructed by a membrane or cyst rather than by stenosis; 3) severe malformations of the cerebral hemispheres including hydranencephaly, significant segments of undeveloped brain, or schizencephaly; 4) myelomeningocele, encephalocele, Dandy-Walker complex, or tumor; or 5) previous shunt insertion. The time to treatment failure was analyzed using the Kaplan-Meier method to construct survival curves. Log-rank (Mantel-Cox) and Gehan-Breslow-Wilcoxon tests were used to determine whether differences between the 2 treatment groups were significant. Results Thirty-five patients met the study criteria. Endoscopic third ventriculostomy alone was performed in 12 patients (mean age 4.7 months), and combined ETV-CPC was performed in 23 patients (mean age 3.5 months). For patients without treatment failure, the mean and median follow-ups were, respectively, 51.6 and 48.0 months in the ETV group and 31.2 and 26.4 months in the ETV-CPC group. Treatment was successful in 48.6% of the patients who underwent ETV alone, as accurately predicted by the Endoscopic Third Ventriculostomy Success Score (ETVSS), and in 81.9% of the patients who underwent ETV-CPC (p = 0.0119, log-rank test; p = 0.0041, Gehan-Breslow-Wilcoxon test; HR 6.42 [95% CI 1.51-27.36]). Conclusions Combined ETV-CPC is significantly superior to ETV alone for infants younger than 1 year of age with congenital aqueductal stenosis. The fact that the outcome for ETV alone was accurately predicted by the ETVSS suggests that these results are applicable in developed countries.     

Rhombencephalosynapsis as a cause of aqueductal stenosis: an under-recognized association in hydrocephalic children

Background

Rhombencephalosynapsis is a rare genetic aberration characterized by variable vermian hypoplasia/aplasia in conjunction with united cerebellar hemispheres. Genetic defects in the isthmic organizer at the mesencephalic–metencephalic junction are presumably responsible for the associated aqueductal stenosis.

Objective

We performed a retrospective review of 20 children with rhombencephalosynapsis to evaluate for and emphasize the association of aqueductal stenosis and hydrocephalus.

Materials and methods

We retrospectively reviewed the MR and CT images of 20 children (0–11 years old) with rhombencephalosynapsis encountered at two academic children’s hospitals. Rhombencephalosynapsis spectrum severity was graded based on pre-existing literature. We analyzed examinations for ventriculomegaly and degree of aqueductal stenosis. The collicular distances were measured from the collicular apices. Imaging studies were also analyzed for malformations of cortical and cerebellar development.

Results

Thirteen of the 20 children (65%) with rhombencephalosynapsis presented with clinical or imaging evidence of hydrocephalus and aqueductal stenosis, principally involving the caudal cerebral aqueduct. All children with aqueductal stenosis had collicular fusion. All six children with complete rhombencephalosynapsis had aqueductal stenosis. The cerebral aqueduct varied from normal to stenotic in children with incomplete rhombencephalosynapsis. Corpus callosum dysgenesis was present in four children.

Conclusion

Aqueductal stenosis in the setting of rhombencephalosynapsis is an under-recognized cause of noncommunicating hydrocephalus. Our findings support the hypothesis that a defect involving the common gene(s) responsible for the differentiation and development of both the roof plate and midline cerebellar primordium at the mesencephalon/first rhombomere junction may be responsible for the association of aqueductal stenosis and rhombencephalosynapsis.     

Regional Ependymal Upregulation of Vimentin in Chiari II Malformation,Aqueductal Stenosis,and Hydromyelia

Vimentin, glial fibrillary acidic protein (GFAP) and S-100 protein were studied by immunocytochemistry in the ependyma of patients with Chiari II malformations, congenital aqueductal stenosis, and hydromyelia. Paraffin sections of brains and spinal cords of 16 patients were examined, 14 with Chiari II malformations, most with aqueductal stenosis and/or hydromyelia as associated features, and 2 patients with congenital aqueductal stenosis without Chiari malformation. Patients ranged in age from 20-wk gestation to 48 years. The results demonstrated: 1) in the fetus and young infant with Chiari II malformations, congenital aqueductal stenosis, and hydromyelia, vimentin is focally upregulated in the ependyma only in areas of dysgenesis and not in the ependyma throughout the ventricular system; 2) GFAP and S-100 protein are not coexpressed, indicating that the selective upregulation of vimentin is not simple maturational delay; 3) vimentin upregulation also is seen in the ependymal remnants of the congenital atretic cerebral aqueduct, not associated with Chiari malformation; 4) in the older child and adult with Chiari II malformation, vimentin overexpression in the ependyma becomes more generalized in the lateral ventricles as well, hence evolves into a nonspecific upregulation. The interpretation from these findings leads to speculation that it is unlikely that ependymal vimentin is directly involved in the pathogenesis of Chiari II malformation, but may reflect a secondary upregulation due to defective expression of another gene. This gene may be one of rhombomeric segmentation that also plays a role in defective programming of the paraxial mesoderm for the basioccipital and supraoccipital bones resulting in a small posterior fossa. This interpretation supports the hypothesis of a molecular genetic defect, rather than a mechanical cause, as the etiology of the Chiari II malformation.     

X-linked hydrocephalus. Further observations

The neuropathologic findings in a case of hydrocephalus of the X-linked recessive aqueductal stenosis type have been studied and compared with those previously reported from the same pedigree as well as with other cases from the literature. Additional pathological findings not previously recorded included: absence of the septum pellucidum and corpus callosum with malformation of the corpora quadrigemina and partial midline fusion of the fornices and thalami and fusion of thalamus with basal ganglia. These new findings indicate a broader phenotypic spectrum of this form of congenital X-linked recessive aqueductal stenosis than was previously known. Additional data from a diagnostic/genetic study of severely mentally retarded individuals are cited to show that 4 out of 5 familial cases of hydrocephalus without spina bifida are compatible with X-linked inheritance.Supported by USPHS Grants GM15422, GM20130 and 5KO4 HD18982. Paper No. 1785 from the University of Wisconsin Genetics Laboratory.     

Bobble-head doll syndrome

A new case of Bobble-head doll syndrome with aqueductal stenosis is presented in a 14 year-old boy. Ventriculocisternostomy performed 8 years after the onset of the abnormal movement resulted in moderate reduction of the head bobbling. Twenty-two cases were found in a review of the literature. In all cases there was a chronic slowly progressive hydrocephalus with usually a cyst of the third ventricle; aqueductal stenosis was less frequent. When recorded, psychomotor development was impaired. Treatment is neurosurgical. Pathogenesis remains unknown.     

Experimental Hydrocephalus in Suckling Hamster Induced by Myxovirus Infection

Abstract This study was undertaken to elucidate the pathogenesis of the hydrocephalus and aqueductal stenosis induced by intracerebral mumps virus inoculation in suckling hamsters.
Mild ventricular dilatation became apparent after 5 days of inoculation. Focal denuding of the ependymal layer and subsequent aqueductal stenosis were observed by 14 days after inoculation. The virus antigen was detected not only in the ependymal cells and choroid plexus, but also in some neurons in the cerebral cortex, hippocampus, midbrain and cerebellum. In the cerebral aqueduct, the orderly arrangement of the cilialy clusters was destroyed on the 5th day after inoculation. After 10 days, proliferation of GFAP positive cells was noticed around the cerebral aqueduct and subsequently caused aqueductal stenosis. In the advanced state of hydrocephalus, the cerebellum was displaced downward and showed an elongated, atrophic and sleevelike structure similar to the Arnold-Chiari malformation. It was suggested that the extensive damage of the ependymal cilia may account for early ventricular dilatation, and subsequent aqueductal stenosis with glial proliferation is the main cause of the advanced hydrocephalus. It has not yet been determined whether the mumps virus can pass through the human placenta or not. If it can, however, our results strongly suggest that mumps virus infection in the human fetus will cause congenital hydrocephalus.     

Neuropathology of central respiratory dysfunction in infancy.

We studied the neuropathology of 7 infants who had primary respiratory problems unrelated to increased intracranial pressure. These infants ranged in age from newborn to 2 years. Five were male. In 2 of them the main neuropathological findings were in the brainstem with prominent neuroglial heterotopia in the subarachnoid space, and aplasia of the VI and VII cranial nerves. Two infants had abnormalities of the X and XII nerves together with neuronal heterotopia and migration failure of the inferior olivary nuclei. In 1 infant diagnosed with Ondine's curse, examination showed diffuse neuronal loss and gliosis in the medullary tegmentum. One infant had a unilateral infarction in the medulla and another showed extensive gliosis in the brainstem tegmentum along with a large infarction in the region of the anterior cerebral artery. These infants exhibited a spectrum of abnormalities including neuronal dysplasia, gliosis and hypoxic-ischemic changes. In the differential diagnosis of respiratory dysfunction in infants a rare consideration is a central etiology based on malformation of essential neuronal components of the brainstem.     

脑白质损伤早产儿血清髓鞘碱性蛋白和S1OOB蛋白的变化及与预后的关系

目的 探讨脑白质损伤( periventricular leukomalacia,PVL)患儿血清髓鞘碱性蛋白(myelin basic protein,MBP)及S100B蛋门(S100B protein,S100B)的动态变化及其与患儿预后的关系.方法 对2007年11月至2008年7月我院住院的78例PVL早产儿(PVL组)和43例正常早产儿(正常对照组),分别在其生后第1、3、7、14天测定血清中MBP及S100B含量.30例正常早产儿及69例PVL患儿出院后每3个月随方1次,直至纠正胎龄至1岁,用Gesell发育量表测定其智力以及运动发育情况.结果 (1) PVL组患儿血清MBP于生后第1天升高[(7.61±1.78) μg/L]、第3天达峰值[( 14.53±3.12) μg/L],后随病情好转,逐渐降低;与正常对照组比较,PVL组患儿在生后第1、3、7、14天血清MBP水平均明显高于正常对照组(P＜0.05).(2) PVL组患儿血清S100B水平在生后第1、3、7天明显升高[(3.82±0.68),(4.41±0.91),(5.78±1.54) μg/L],第7天达峰值,与正常对照组比较,差异有统计学意义(P＜0.05);至生后第14天时,S100B明显降低,两组比较已无明显差异(P＞0.05).(3) PVL组患儿生后第7天血清S100B、MBP持续升高者,随访至1岁时其发育商比生后第7天血清S100B及MBP明显下降者落后;也明显落后于正常早产儿(P＜0.05).结论 PVL患儿生后血清MBP及S100B水平与病情严重程度相关.如患儿血清MBP及S100B持续升高超过7d,则发育商明显落后,预后不良.     

Pyogenic meningitis: sonographic evaluation.

Forty infants with proven pyogenic meningitis were evaluated by real time cranial sonography. A spectrum of sonographic abnormalities was observed which included echogenic sulci, focal or diffuse increase in parenchymal echoes, ventriculitis, ventriculomegaly with or without aqueductal block, subdural collection, parenchymal infarcts, abscess and subdural empyema. There were two infants with normal sonogram while encephalomalacia was seen in another two patients. An excellent correlation was observed between clinical profile, cerebrospinal fluid biochemistry and sonographic findings.     

Gliomas of the tectum and periaqueductal region of the mesencephalon.

Gliomas that arise in the tectal and periaqueductal region of the mesencephalon usually present with hydrocephalus secondary to occlusion of the aqueduct of Sylvius. A review of 486 brain tumors in children treated during a 5-year period revealed 6 children with gliomas of the tectal plate. The 6 children were shunted for hydrocephalus, presumed secondary to aqueductal stenosis, prior to establishing the diagnosis of tectal plate glioma. No abnormalities were noted on the initial, uncontrasted computed tomography (CT) scans. The tumors are isodense without contrast enhancement which makes the CT diagnosis difficult. Magnetic resonance imaging (MRI) is diagnostic and demonstrates the characteristic enlargement of the tectum with increased density on T2 images. T1 density and gadolinium enhancement are variable. Pathological confirmation was obtained by open biopsy in 2 patients, a stereotaxic biopsy was performed on 2 children; 2 children were not biopsied. The tumor histology obtained was that of pilocytic astrocytoma. Two patients were treated with radiation therapy at the time of diagnosis. One child was followed closely and subsequently irradiated after tumor progression. All patients in this series are alive and functioning adequately 2-10 years after the onset of symptoms.     

Extensive and partial protein hydrolysate preterm formulas: the effect on growth rate, protein metabolism indices, and plasma amino acid concentrations

BACKGROUND: The use of protein hydrolysate preterm formulas is restricted because data on their nutritional adequacy are scarce. The authors evaluated the rate of growth and indices of protein metabolism in low-birth weight infants fed extensive and partial protein hydrolysate preterm formula followed for 12 weeks. METHODS: A total of 61 low-birth weight infants were assigned randomly to receive extensive protein hydrolysate preterm formula (EH: n = 16), partial protein hydrolysate preterm formula (PH: n = 15), and standard preterm formula (SF; n = 15), or were fed their own mother's fortified breast milk (FBM; n = 15). The infants were investigated at study entry, and at 4, 8, and 12 weeks after study entry. RESULTS: There were no differences with respect to growth rate (weight gain, increments in length and head circumference), urea, albumin, prealbumin, transferrin, and plasma amino acid concentrations (except for tyrosine on a single occasion) according to the degree of hydrolysis. There were also no differences between groups fed hydrolyzed formulas and SF. However, several differences were found when EH and PH were compared with FBM. Weight gain from the entry to 12 weeks, serum urea at 12 weeks, and total plasma essential amino acids at 8 weeks were significantly higher in groups fed EH and PH than in those fed FBM. In addition, valine was significantly higher in groups fed PH (P < 0.05) than in the group fed FBM at 8 and 12 weeks, tyrosine was higher in EH and PH in comparison with FBM at 4 weeks, and in PH versus FBM at 12 weeks after study entry. CONCLUSIONS: This study suggests that experimental EH and PH are at least nutritionally equivalent to SFs.     

Pyloric stenosis and eosinophilic gastroenteritis in infants

Eosinophilic gastroenteritis is known to cause gastric outlet obstruction in adults, but has been reported only rarely in infants presenting with pyloric stenosis, a common form of gastric outlet obstruction in children. We describe two infants who presented with classic clinical and radiographic evidence of pyloric stenosis and who were found to have histologic evidence of eosinophilic gastroenteritis on gastric antral biopsies. Their presentation is compared with the clinical and laboratory findings of 47 other infants with pyloric stenosis.     

Visual pathway tumors and hydrocephalus

The authors evaluated the impact of hydrocephalus on the clinical picture of children with visua pathway tumor (VPT) with or without neurofibromatosis (NF).Charts of children with VPT treated in the authors' center since 1985 were retrospectively reviewed, and those with hydrocephalus were selected and summarized. Thirty-five children with VPT were found, of whom 20 had NF.Hydrocephalus was found in 4 children with NF (20% ) and in 5 without NF (33.3% ). In 6 ofthechildren, ventricular dilatation with signs of acute increased intracranial pressure already existed at the time of diagnosis and the hydrocephalus was shunted at this time. In the other 3 children, all with NF,the hydrocephalus resulted from slowly developing aqueductal stenosis, leading in 2 to severe visual acuity deterioration. The results suggest that in children with VPT and NF, hydrocephalus, and especially hydrocephalus resulting from aqueductal stenosis, is more frequent than in the general population of NF patients, and less frequent than in VPT patients without NF. The possibility of the indolent development of hydrocephalus should be borne in mind while following children with NF. The optic nerve, when already involved with a glioma, is more vulnerable to increased pressure. Thus, in children with VPT and NF, any ventricular dilatation should lead to a consideration of early shunting.     

Aqueductal stenosis presenting as isolated tremor: case report and review of the literature

Essential tremor is rare in children, particularly in the absence of a significant family history. We report the case of a child with compensated hydrocephalus secondary to aqueductal stenosis whose sole presenting symptom was tremor. An otherwise healthy 6-year-old male developed a fine hand tremor, which over the course of 4 years both increased in intensity and spread to involve the lower limbs and head. After an MRI had confirmed hydrocephalus due to aqueductal stenosis, the patient underwent an endoscopic third ventriculostomy. His tremor improved markedly, but did not completely resolve. Occult hydrocephalus should be considered in the differential diagnosis of new-onset tremor. Progression of the tremor should halt with treatment of the hydrocephalus, and clinical improvement may be seen.     

Mumps meningitis: electroencephalography and leukocyte migration inhibition by basic myelin protein

In 20 patients with mumps meningitis, electroencephalography and leukocyte migration inhibition tests with basic myelin protein were carried out. Fourteen patients had mild or moderate EEG abnormalities indicative of encephalitis as well. Cellular reactivity to basic myelin protein was found in 4 cases only. The observations support the concept that mumps meningoencephalitis is a consequence of a direct viral impact onto the nervous tissue, i.e. no neuroallergic mechanisms are involved.     

The neurochemistry of phenylketonuria

The mechanisms by which deficiency of hepatic phenylalanine hydroxylase causes central nervous system disease are reviewed. The neurological disease appears to be secondary to increased concentrations of phenylalanine and a decrease in the concentrations of other large neutral amino acids, especially methionine and tyrosine, within the central nervous system. This causes a deficiency of the neurotransmitter dopamine, reduced protein synthesis and demyelination. Similar mechanisms appear to be operating when blood phenylalanine concentrations are in the range expected for early continuously treated phenylketonuria. Conclusion The severe brain disease found in phenylketonuria is caused by a raised blood phenylalanine content which increases the brain free phenylalanine and decreases the concentration of other large neutral amino acids. Brain protein synthesis is decreased, myelin turnover is increased and there are abnormalities in amine neurotransmitter systems.     

Neurotrophins and tonsillar hypertrophy in children with obstructive sleep apnea

Enlarged adenotonsillar tissue (AT) is a major determinant of obstructive sleep apnea (OSA) severity in children; however, mechanisms of AT proliferation are poorly understood. We hypothesized that early exposure to respiratory syncytial virus (RSV) may modify AT proliferation through up-regulation of nerve growth factor (NGF)-neurokinin 1 (NK1) receptor dependent pathways. AT harvested from 34 children with OSA and 25 children with recurrent tonsillitis (RI) were examined for mRNA expression of multiple growth factors and their receptors. In addition, NK1 receptor expression and location, and substance P tissue concentrations were compared in AT from OSA and RI children. NGF mRNA and its high-affinity tyrosine kinase receptor (trkA) expression were selectively increased in OSA (p<0.001). NK1 receptor mRNA and protein expression were also enhanced in OSA (p<0.01), and substance P concentrations in OSA patients were higher than in RI (p<0.0001). AT from OSA children exhibit distinct differences in the expression of NGF and trkA receptors, NK1 receptors, and substance P. The homology between these changes and those observed in the lower airways following RSV infection suggests that RSV may have induced neuro-immunomodulatory changes within AT, predisposing them to increased proliferation, and ultimately contribute to emergence of OSA.     

早产儿血清促红细胞生成素水平与脑损伤的关系

目的 探讨早产儿血清促红细胞生成素（EPO）水平与脑损伤的关系。方法 选取2014 年10月至2015 年9 月出生胎龄在28~34 周的早产儿304 例作为研究对象。采用颅脑B 超和MRI 检查诊断脑损伤,ELISA 检测血清EPO、S100 蛋白、神经元特异性烯醇化酶（NSE）和髓鞘碱性蛋白（MBP）水平,比较不同血清EPO 水平早产儿脑损伤的发生率,分析血清EPO 水平与各指标的相关性;采用多因素Logistic 回归分析研究血清EPO 水平与脑损伤的关系。结果 304 例早产儿中发生脑损伤125 例（41.1%）;低水平EPO 组缺血性脑损伤发生率明显高于中高水平EPO 组（P P P P 结论 血清EPO 低水平的早产儿脑损伤发生率高,血清EPO 水平与早产儿脑损伤密切相关。     

Association of changes in bombesin immunoreactive neuroendocrine cells in lungs of newborn infants with persistent fetal circulation and brainstem damage due to birth asphyxia

The pulmonary neuroendocrine (NE) cells, from 16 term infants dying at 1-4 days of age from birth asphyxia, were immuno stained for bombesin-like immunoreactivity by the immunoperoxidase method. The distribution and frequency of bombesin-immunoreactive NE cells were quantified morphometrically and correlated with the presence or absence of brainstem function and persistent fetal circulation (PFC). In infants with loss of brainstem function, the frequency of bombesin immunoreactive NE cells was significantly increased compared to infants with intact brainstem function, i.e. meconium aspiration with PFC. Infants with brainstem injury, with one exception, failed to develop PFC. Pathological changes in the tegmentum of the brainstem, i.e. containing the respiratory center, correlated in nine of 10 cases with loss of brainstem function. These data suggest an inverse relationship between brainstem function, release of bombesin-like peptide from the pulmonary NE cells and the functional state of the pulmonary vasculature. Intact brainstem function appears to be essential for both the release of bombesin-like peptide from the NE cells and for pulmonary vasoconstriction leading to PFC; absence of brainstem function is, on the other hand, associated with failure to release bombesin-like peptide and loss of PFC type reactivity in the pulmonary vasculature. However, it appears unlikely that bombesin itself is a direct mediator of pulmonary vasoconstriction.