脑性盐耗综合征与抗利尿激素异常分泌综合征的鉴别

脑性盐耗综合征和抗利尿激素异常分泌综合征在颅脑疾病相关的低钠血症中均占用一定比例.两种疾病临床表现极为相似,且易混淆,而治疗原则却大不相同.因此,正确鉴别两种疾病,对于临床患者的治疗及预后意义重大.该文从发病机制、诊断及治疗等方面对两种疾病进行鉴别.     

Rapid deterioration of primary fourth ventricular outlet obstruction resulting in syndrome of inappropriate antidiuretic hormone secretion

Fourth ventricular outlet obstruction (FVOO) is a rare cause of obstructive hydrocephalus. Although FVOO accompanied by malformative syndrome and secondary causes of obstruction are common, there are few reports of primary FVOO (PFVOO). The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a rare presenting feature of hydrocephalus. A 1‐year, 8‐month‐old boy with a normal head circumference developed SIADH accompanied by rapid deterioration of symptoms of intracranial hypertension. PFVOO was diagnosed because magnetic resonance imaging revealed an enlarged ventricular system with a barely visible membranous obstacle at the foramen of Magendie. All symptoms were resolved by endoscopic third ventriculostomy. PFVOO should be considered as a rare form of congenital obstructive hydrocephalus, especially in patients with tetraventricular hydrocephalus. To the best of our knowledge, this is the first case of an infant with SIADH, resulting from acute deterioration of non‐tumoral raised pressure hydrocephalus.     

Human herpesvirus-6 infection in neonates: Not protected by only humoral immunity

BACKGROUND: Infants are usually protected from various viral infections, including human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) infections, during the early infantile period by antibodies transferred from their mothers. However, rare cases of exanthem subitum (ES) in neonates have been described in published reports. METHODS: From the infantile patients of febrile illness, HHV-6 and HHV-7 DNA were examined by the polymerase chain reaction method. Antibodies to HHV-6 and HHV-7 were detected by indirect immuno-fluorescence assay and neutralization test. Viral isolation was attempted from the patient's peripheral blood mononuclear cells (PBMC) during the acute phase of febrile illness. RESULTS: Human herpesvirus-6 was verified virologically in two neonates who were clinically diagnosed as ES within the first month of life. Although high copies of HHV-6 DNA were detected in their PBMC during the acute phase, the isolation of HHV-6 from their PBMC was not successful. Neutralizing antibodies to HHV-6 were detected in sera of the acute phase, and those antibodies were considered to be transferred from their mothers. Antibody titers showed fourfold elevation in sera of the convalescent phase. The HHV-6 infection occurred despite the presence of pre-existing maternal antibody. Human herpesvirus-7 and HHV-7 DNA were not detected from their clinical samples. CONCLUSIONS: This observation suggests that HHV-6 infection could not be protected by only humoral immunity.     

Distribution of human herpesvirus 6 and varicella-zoster virus in organs of a fatal case with exanthem subitum and varicella

The distribution of human herpesvirus 6 (HHV-6) and varicella-zoster virus (VZV) was examined in autopsy samples from a fatal case with both virus infections. A 9-month-old boy developed convulsive seizures followed by macular skin rashes, rapidly progressed to brain death, and died 15 days after the onset, when signs of varicella were noted. An isolation of HHV-6 from blood and evaluation of antibody activities to various viral agents including HHV-6 were performed before his death. Postmortem examinations included: (i) isolation of HHV-6 and VZV from tissues or organs; (ii) detection of both virus antigens in tissues or organs by an indirect immunofluorescent assay using monoclonal antibodies to both viruses; (iii) amplification of both viruses and human herpesvirus 7 DNA sequences by a nested polymerase chain reaction assay; and (iv) endonuclease digestion of amplified products of HHV-6 DNA for differentation of variants A and B. Human herpesvirus 6 DNA was detected in peripheral blood mononuclear cells (PBMC) and plasma obtained at the eruptive stage but present only in PBMC 15 days after, indicating the primary infection with HHV-6, although the virus was not isolated from the same blood sample and a significant rise in the antibody titers to HHV-6 was not observed. Both virus antigens and DNA were detected in various tissues or organs obtained at autopsy, but only VZV was isolated from these samples, suggesting disseminated infection with both viruses in an infant. All the amplified products of HHV-6 DNA were variant B. Among the findings for the distribution of virus antigens, it was noteworthy that HHV-6 antigen was demonstrated in the endothelial cells of small vessels in the frontal lobe of the brain. There was no evidence of HHV-7 infection. These data indicate that the primary HHV-6 infection closely followed by the primary VZV infection had the potential hazard of an unexpected and apparently life-threatening event, in which disseminated infections with both viruses were noted in multiple tissues or organs including the brain.     

Syndrome of inappropriate anti‐diuretic hormone in Kawasaki disease

Background: The pathogenesis of hyponatremia in acute Kawasaki disease (KD) remains unclear. A recent case report of KD complicated by syndrome of inappropriate anti‐diuretic hormone (SIADH) led us to determine the prevalence of SIADH in acute KD patients. Methods: Subjects were 39 Japanese KD patients (2–84 months of age, 25 males and 14 females) treated with intravenous immunoglobulin (IVIG), 2 g/kg/day and oral aspirin. SIADH was defined when hyponatremic patients (serum sodium concentration <135 mEq/L) had decreased serum osmolality <280 mOsm/kg H₂O, elevated urine sodium concentration >20 mEq/L and elevated urine osmolality >100 mOsm/kg H₂O without dysfunctions of renal, thyroid or adrenal gland. We also studied the relation between clinical course of SIADH and the amount of infused fluid during IVIG. Results: Before IVIG, 27 patients (69%) had hyponatremia and 11 (28% of total; 41% of hyponatremic patients) had SIADH while after IVIG, 13 (33%) hyponatremia and four (10%; 31% of hyponatremic patients) SIADH. Among 11 patients with SIADH before IVIG, SIADH improved in 10 after IVIG, but hyponatremia persisted in five. Significant correlation was observed between serum sodium concentration after IVIG and infusion amount in SIADH patients (r=?0.64, P= 0.03), but not in non‐SIADH patients. Conclusions: This is the first report to show that SIADH is common as a cause of hyponatremia in acute KD and hence careful management of water and sodium is warranted.     

Central Diabetes Insipidus and Cisplatin‐Induced Renal Salt Wasting Syndrome: A Challenging Combination

We describe a 2‐year‐old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin‐induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin‐induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury.     

Oral urea for the treatment of chronic syndrome of inappropriate antidiuresis in children

We report the successful use of oral urea in the management of children with chronic syndrome of inappropriate antidiuretic hormone secretion (SIAD). We performed a retrospective review of four children with chronic SIAD. After initial attempts at management with fluid restriction, each was started on a 30% to 50% oral urea solution, and the dose was titrated until normal serum sodium was achieved. Fluid intake was liberalized after serum sodium normalization. All four children normalized their serum sodium. No side effects or toxicities were experienced. Oral urea is a safe, effective treatment for chronic SIAD in children.     

Five cases of thrombocytopenia induced by primary human herpesvirus 6 infection

Abstract Five patients suffering from exanthem subitum with thrombocytopenia were confirmed as primary human herpesvirus 6 (HHV-6) infection by serological test. All cases had thrombocytopenia during the acute phase of exanthem subitum. The clinical features of these cases were benign, and all recovered without any specific treatment. Moreover. 4 of the 5 cases showed a mild elevation of hepatic transaminase during the same period, and other viral infections including cytomegalovirus, Epstein-Barr virus, and human herpesvirus 7 were ruled out in these patients. It was speculated that direct inhibition of platelet production by the virus or cytokine induced by the virus-infected cells was the mechanism of the thrombocytopenia induced by primary HHV-6 infection.     

Primary infections of human herpesvirus-7 and herpesvirus-6: a comparative, longitudinal study up to 6 years of age

In order to understand the infection status of human herpesvirus 7 (HHV-7) in Taiwan and clarify the serological cross-reactivity between HHV-7 and HHV-6, a longitudinal study was carried out in 52 infants from whom 9 sera were available from birth to 6 years of age. All sera were tested for antibodies against HHV-6 and HHV-7 by indirect immunofluorescence assay. HHV-7 infection was not seen before 6 months of age and gradually emerged thereafter, reaching a cumulative rate of 28.8%, 67.3%, 73.1 %, 78.8%, 82.7%, and 86.5% by the ages of 1. 2, 3, 4, 5 and 6 years, respectively. Primary HHV-6 infection induced a reactive HHV-7 antibody in 10/28 (35.7%) cases with a titre of no more than 10. Twenty-eight children (53.8%) were infected by HHV-6 earlier than HHV-7. while eight (15.4%) were infected by HHV-7 earlier than HHV-6. In summary, HHV-7 infected children later than HHV-6. A one-way cross-reaction of HHV-7 serology by HHV-6 was revealed and a titre of 20 is appropriate for defining HHV-7 infection.     

人疱疹病毒6型荧光定量分型方法的建立和临床应用

目的 建立对人疱疹病毒6型(HHV-6)能同时进行定量和分型的荧光定量PCR检测新方法,运用该方法对临床疑似病毒性脑炎患儿进行检测.方法 以HHV-6聚合酶基因区(U38)为靶序列,设计通用引物和特异性分型探针,建立能同时检测HHV-6型A/B亚型的荧光定量PCR方法,进行敏感性和特异性实验.对临床445例疑似脑炎患儿的脑脊液标本进行HHV-6荧光定量分型检测,阳性结果测序验证.结果 HHV-6A和HHV-6B病毒株荧光定鼍分型检测结果均为阳性,两亚型之间无交叉.单纯疱疹病毒1型和2型、水痘-带状疱疹病毒、巨细胞病毒、爱泼斯坦.马尔病毒、乙肝病毒、金黄色葡萄球菌、肺炎支原体、人类基因组DNA及空白对照均为阴性.HHV-6荧光定量分型最低能检测到10拷贝/μl HHV-6A/B.在临床445例疑似脑炎患儿脑脊液标本中检出HHV-6阳性21例(4.72%),其中HHV-6A阳性4例,HHV-6B阳性16例,HHV-6A和HHV-6B混合感染1例.整个PCR操作过程2-3 h.结论 HHV-6荧光定量分型方法能对HHV-6同时进行定量和分型,具有特异、敏感、简便、快速的特点,可为临床HHV-6感染性脑炎提供早期、敏感的诊断依据.     

Crouzon综合征合并生长激素缺乏症1例报告及重组人生长激素治疗随诊

目的报告1例Crouzon综合征合并生长激素缺乏症(GHD)患儿及其重组人生长激素(rhGH)治疗结果。方法回顾分析患儿以rhGH治疗2年的临床资料。结果患儿女性,5岁4月龄时身高98.2 cm(P_3),有特殊面容(舟状头、突眼、反颌畸形等)。基因检测示FGFR2基因存在c.1061CG(p.Ser354Cys)杂合变异,源自母亲,为已知的致病变异,诊断为Crouzon综合征。同时相关检查提示患儿合并GHD。给予rhGH治疗2年,身高117 cm,平均生长速率为9.4 cm/a。治疗期间,头颅磁共振监测提示侧脑室及第三脑室略扩张等表现未进展,眼科随诊示左眼视盘水肿程度较前减轻,未发现不良反应。结论矮小可能是Crouzon综合征的表型,rhGH治疗可以改善Crouzon综合征合并GHD患儿的身高,且未引起患儿颅内压增高等不良反应。     

Differentiating inherited human herpesvirus type 6 genome from primary human herpesvirus type 6 infection by means of dried blood spot from the newborn screening card

To differentiate active human herpesvirus type 6 (HHV-6) infection from inherited HHV-6 (iHHV-6), we analyzed dried blood spots from archived newborn screening cards in 3 patients with high HHV-6 DNA copy numbers. Two patients were positive for HHV-6 DNA as neonates suggesting iHHV-6. In 1 patient, the absence of HHV-6 DNA excluded iHHV-6.