Cerebral thrombosis in childhood nephrosis

Sinovenous thrombosis is an uncommon but serious complication associated with nephrotic syndrome in children. We describe a 9-year-old Caucasian boy who presented with dehydration, vague neurological symptoms and seizures. A diagnosis of nephrotic syndrome was made during the course of hospitalization. The serum antithrombin III level was decreased and brain imaging showed cerebral sinovenous thrombosis. Anticoagulant therapy with heparin was commenced and the patient made a slow but gradual clinical, as well as radiological recovery. We describe this case and review available literature to highlight the importance of suspecting and recognizing this potentially life threatening complication and initiating early treatment.     

儿童原发性肾病综合征合并颅内静脉血栓4例病例报告

目的 通过对原发性肾病综合征合并颅内静脉血栓患儿行临床分析,探讨儿童NS合并颅内静脉血栓早期诊断和治疗的可行方案。方法 纳入2012年1月至2015年9月在上海市儿童医院住院的原发性肾病综合征且经头颅CT和（或）MRI确诊的颅内静脉血栓患儿,对其临床症状、实验室指标、影像学检查结果、疗效及预后进行分析。结果 4例原发性肾病综合征合并颅内静脉血栓患儿进入分析,均为男性,年龄5岁4个月至11岁4个月,出现颅内静脉血栓时间距原发性肾病综合征起病时间为1个月至7年余。4例颅内静脉血栓发病时均有神经精神系统症状,查体均未见神经系统阳性体征。3例在颅内静脉血栓发病期间D-二聚体、纤维蛋白原降解产物（FDP）均升高,抗凝血酶Ⅲ（AT-Ⅲ）下降;确诊后D-二聚体、FDP较前继续升高; 4例血清白蛋白明显降低,总胆固醇明显升高。4例出现颅内静脉血栓临床症状当日或次日均行头颅MRI增强+MRV+MRA检查,3例为左侧乙状静脉窦血栓,1例为脑栓塞。明确颅内静脉血栓诊断后,3例予尿激酶溶栓,低分子肝素钙和双嘧达莫抗凝治疗;1例脑栓塞患儿予对症和抗凝治疗;4例症状均明显改善。3例出院后6~12个月随访头颅MRI增强+MRV显示颅内异常信号均有不同程度吸收。结论 儿童原发性肾病综合征合并 颅内静脉血栓易发生于左侧乙状静脉窦。在原发性肾病综合征病程中如出现神经精神系统症状时,应及时行头颅MRI相关序列检查,有助于颅内静脉血栓早期诊断;早期积极溶栓治疗预后良好。     

Mastoiditis,meningitis and venous sinus thrombosis caused byFusobacterium necrophorum

The authors report a case of septic venous sinus thrombosis (VST) and meningitis occurring as an early complication of mastoiditis caused byFusobacterium necrophorum. CT scan was normal, and cerebral angiography was required to diagnose the VST. The evolution was favourable with appropriate antimicrobial therapy and steroids.     

Co‐existence of renovascular hypertension,polyarteritis nodosa,antiphospholipid syndrome and methylenetetrahydrofolate reductase mutation

We present a hypertensive child with a co‐existence of polyarteritis nodosa, anti‐phospholipid antibodies (aPL), methylenetetrahydrofolate reductase (MTHFR) mutation and increased lipoprotein a level. Elevated renin, aldosterone and aPL levels, micro‐aneurysms, occlusion and thrombosis at left and right renal artery were found. Anti‐hypertensive agents, prednisolone and pulse cyclophosphamide therapy were started and a stent was inserted in the left renal artery. Two months later, brain magnetic resonance imaging/magnetic resonance imaging angiography showed acute infarct area of the left parietofrontal lobe and middle cerebral artery stenosis. We found bilateral peripheral neuropathy, persistent aPL and elevated Lp(a) level and heterozygous A1298C/MTHFR mutation. Intravenous immunoglobulin and low‐molecular‐weight heparin treatment was added. In conclusion, our observation suggests that in patients with systemic vasculitis, such as polyarteritis nodosa, aPL are probably associated with greater thrombotic risks. The investigation of the LP(a) levels and MTHFR mutations as a synergic pro‐coagulant effect might also be considered for determining patients with vasculitis at risk for severe thrombotic events.     

Ascitic fluid drainage using a peritoneal dialysis catheter to prevent and treat multi‐organ dysfunction in veno‐occlusive disease in children undergoing hematopoietic stem cell transplantation

Veno‐occlusive disease (VOD), or sinusoidal obstruction syndrome, is a well‐recognised, serious complication associated with the chemotherapy conditioning therapy used in hematopoietic stem cell transplantation (HSCT). Fluid management is typically challenging in children with this condition. We describe effective early use of peritoneal dialysis catheters to drain extravascular, intra‐abdominal fluid in children with VOD, allowing intravascular fluid administration to preserve renal perfusion and function, preventing multi‐organ dysfunction. All but one of the children are long‐term survivors, both of their significant VOD and their HSCT. The child that did not survive died from their underlying metabolic illness, not VOD.     

Infantile polyarteritis nodosa presenting as hyponatraemic hypertensive syndrome

The association of arterial hypertension with hyponatraemic dehydration, known as hyponatraemic hypertensive syndrome (HHS), is a rare and serious hypertensive complication. Here, we describe a 17-mo-old girl who presented with severe hyponatraemic dehydration, hypokalaemia, polyuria, and nephrotic-range proteinuria associated with malignant arterial hypertension and systemic inflammatory disease. Diagnosis of classic polyarteritis nodosa (c-PAN) was made on the basis of renal arteriography demonstrating small arterial aneurysms in association with non-aneurismal changes such as arterial cut-off, arterial tapering stenosis and nephrogram perfusion defect. A decrease of blood pressure by antihypertensive treatment resulted in the normalization of HHS abnormalities. However, c-PAN became well controlled only after 4 mo of immunosuppressive therapy. CONCLUSION: The main interest of this case was the uncommon presentation of systemic polyarteritis nodosa in a very young child. Renal ischaemia from intrarenal vessel disease may have been the trigger event for HHS in our case. Management of PAN-associated severe arterial hypertension is based on immunosuppressive and antihypertensive treatment.     

Factor V Leiden and prothrombin 21210G>A mutation and paediatric ischaemic stroke: a case–control study and two meta‐analyses

Aim: To determine whether factor V Leiden (FVL) and prothrombin (PT) 20210G>A mutation are associated with paediatric ischaemic stroke. Methods: The study consisted of two parts. Case–control study included neuroradiologically confirmed paediatric ischaemic stroke patients from two tertiary children’s hospitals in Estonia. For control group, DNA was obtained from 400 anonymous screening test cards of newborns born consecutively in all delivery departments of Estonia in January 2005. Meta‐analyses was performed to assess the association between paediatric sinovenous thrombosis and FVL and PT 20210G>A. Results: A total of 75 children (45 boys, 30 girls) were included into the case–control study: 19 with childhood arterial ischaemic stroke, 49 with perinatal arterial ischaemic stroke and seven with cerebral venous thrombosis. Both FVL and PT 20210G>A occurred significantly more frequently among patients with sinovenous thrombosis compared with controls (OR = 12.9; 95% CI: 2.3–73.0 and OR = 11.9; 95% CI: 2.1–67.2, respectively). The difference was not significant between childhood/perinatal arterial ischaemic stroke and controls. Meta‐analyses (including our study) revealed that both FVL and PT 20210G>A are associated with paediatric sinovenous thrombosis (OR = 3.1; 95% CI: 1.8–5.5 and OR = 3.1; 95% CI: 1.4–6.8, respectively). Conclusion: FVL and PT 20210G>A are associated with paediatric sinovenous thrombosis.     

Persistent unilateral white‐out in preterm infant

We would like to present a case of persistent right sided collapse in a preterm baby with an unexpected diagnosis. Baby X was born floppy requiring resuscitation and was intubated, ventilated and was transferred to NICU. There was decreased air entry on auscultation of right side of the chest, while the rest of the examination was normal. The chest X‐ray showed right side white‐out suggestive of collapse consolidation. She required significantly high ventilatory pressures to maintain saturations and chest X‐ray performed on day 4 remained unchanged with persistent right sided white‐out. The CT scan of the chest showed no definable right lung, right pulmonary artery or right main bronchus. The diagnosis of right lung agenesis with single pulmonary artery was made and baby was found to have more congenital malformations on further investigations, and later developed complications leading to palliative care.     

Potential pitfalls in imaging of paediatric cerebral sinovenous thrombosis

Paediatric cerebral sinovenous thrombosis (CSVT) is a rare but serious condition. The imaging signs may be subtle with a number of potential pitfalls. We present a pictorial essay of the pitfalls of diagnosis of CSVT on CT and MRI. We describe, using examples, potential pitfalls on both imaging modalities including anatomical variants of the cerebral venous system, extra-axial fluid collections and enhancement of chronic thrombus. Pitfalls particular to CT are discussed including beam-hardening artefact, image windowing and neonatal physiological intravascular hyperdensity. We review the potential variability in the appearance of thrombus on MRI, dependent largely on the stage of thrombus evolution and the pulse sequence. The signal intensity of thrombi, although described as evolving in a typical pattern on T1- and T2-weighted MRI, may be affected by variability in the degree of oxygenation of red cells in the forming thrombus, dilution and secondary propagation of thrombosis. Individual MRI sequences should not be interpreted in isolation, but as a set, and compared with CT images if available.     

Cerebral sinus occlusion in a boy presenting with asparaginase-induced hypertriglyceridemia

Cerebral sinus thrombosis is a rare but severe complication during treatment for acute lymphoblastic leukaemia (ALL). It mostly has been reported during treatment with asparaginase and dexamethasone. Hypertriglyceridemia has - albeit very rarely - also been associated with asparaginase therapy. The combination of cerebral sinus thrombosis and hypertriglyceridemia however, has not yet been reported. Here we describe a 15-year-old boy who presented with clinical symptoms and radiologic findings of a cerebral sinus thrombosis. In addition, a life-threatening hypertriglyceridemia was present. The complication was successfully treated by anticoagulation with low molecular weight heparin and the lipid regulator bezafibrate.     

Changes in pulmonary arterial pressure in term‐infants with hypoxic–ischemic encephalopathy

Background: Hypoxic–ischemic encephalopathy (HIE) is an important complication that results from birth asphyxia or some other adverse conditions and has a high risk of neonatal morbidity and mortality. It is unclear, however, whether the elevated pulmonary arterial pressure (PAP) can aggravate the condition and prognosis of HIE. The purpose of the present study was to investigate the relationship between the changes of PAP and HIE in term infants after birth asphyxia. Methods: The left/right ventricle pre‐ejection phase (LPEP/RPEP), left/right ventricle ejection time (LVET/RVET) and the ratios of LPEP/LVET and RPET/RVET were evaluated in 40 term infants with HIE and 40 healthy controls on days 1, 3, 7, and 12–14 after birth using echocardiogram. PAP such as pulmonary arterial diastolic pressure (PADP, mmHg), pulmonary arterial resistance (PAR, mmHg), and pulmonary arterial resistance/systemic resistance ratio (PAR/RS) was calculated using these indexes. Patient mortality was also evaluated. Results: PADP, PAR, and PAR/RS were significantly higher in HIE patients than in healthy controls during the first week after birth, particularly in severe‐degree HIE patients. And until the end of the first week of life, these indexes may return to the levels of healthy controls. Persistent fetal circulation (PFC) was found in nine patients (7/16 severe, 2/12 moderate HIE patients), and non‐PFC was found in mild HIE patients. Two patients with PFC died. No patients without PFC died. The course of HIE was longer in patients with pulmonary hypertension than in those without. Conclusion: Increased PAP is an important pathophysiological process that may influence the course and prognoses of HIE in infants after birth asphyxia, particular in severe HIE patients who often have PFC. Thus it is important to assess changes in PAP using echocardiography.     

小儿外伤性基底节区脑梗塞37例临床分析

本文报告37例小儿外伤性基底节区脑梗塞诊治体会,临床表现伤后数小时或数天后出现一例肢体锥体束损害,CT示基底节区低密度灶,无明显占位效应,治疗以脱水,扩血管及神经营养药为主,预后良好。     

Urinary excretion of sphingomyelinase phosphodiesterase acid‐like 3b in children with intractable nephrotic syndrome

Rituximab (RTX), a specific antibody to human CD20, has been successfully used to treat intractable nephrotic syndrome (NS). Recent studies have suggested a direct effect of RTX on podocytes by targeting sphingomyelinase phosphodiesterase acid‐like 3b (SMPDL‐3b). Thus, we examined the urinary excretion of SMPDL‐3b as well as its immunoreactivity in biopsy specimens from children with intractable NS. Urine samples from six patients (five with minimal‐change NS and one with focal segmental glomerulosclerosis) and from four healthy adults were examined. Glomerular immunoreactivity and urinary excretion of SMPDL3b in proteinuric NS patients decreased compared with controls. Interestingly, urine samples obtained from the same patients at the remission stage after RTX treatment showed an increase in urinary SMPDL‐3b excretion compared with the proteinuric stage. Urinary excretion level of SMPDL‐3b could thus be used to predict the clinical efficacy of RTX treatment in NS patients.     

Reno‐ and splenoportal anastomosis for a retransplant patient with situs inversus

PV thrombosis following pediatric LT is a serious complication that may lead to graft loss. LDLT poses limitations with regard to the availability of vein grafts for complex PV reconstructions. We herein report a unique reconstruction of the PV inflow in a one‐yr‐old boy with situs inversus undergoing re‐LDLT. The inflow was derived from the SPV and the RRV. A common channel was created utilizing a donor IMV and the recipient explant LHV as vascular conduits. With the application of innovative surgical reconstructions, pre‐existing portomesenteric thrombosis may be amenable to re‐LDLT in the pediatric population.     

Isolated cerebral thrombo-embolism and Crohn disease

Arterial thrombo-embolism is an unusual complication in inflammatory bowel disease in adults and children. Cerebral arterial disease has been reported on only a few occasions. There are only two previous case reports of arterial disease occurring in a child with Crohn disease. However in both instances the arterial disease was part of a generalised Takayasu arteritis which resulted in multi-organ involvement. This report describes a 14-year-old boy who developed seizures before a histological diagnosis ofCrohn disease was made. These seizures were the result of a vascular lesion which was confined to the right middle cerebral artery.Conclusion Crohn disease as well as ulcerative colitis should be considered as a possible cause of cerebrovascular accidents in children     

Gradenigo's syndrome with lateral venous sinus thrombosis: successful conservative treatment

Gradenigo's syndrome (GS) is a rare disease characterised by the triad otitis media, pain in the region innervated by the first and the second division of trigeminal nerve and abducens nerve palsy. Septic sinus thrombosis is one of the most frequent and relevant complication of GS; it is often due to persistent damage and late diagnosis. Computed tomography (CT) scan and magnetic resonance imaging (MRI) allow the correct diagnosis in most cases. Surgical therapy may be necessary for a better and more rapid resolution of the disease. We report the case of a 4-year-old child that was admitted for facial nerve palsy and abducens nerve palsy subsequent to a 2-week persistent pain in the right ear. MRI showed infective acute process of the right mastoid and partial ipsilateral sinus thrombophlebitis. The child was treated with high-dose intravenous antibiotics and with oral anticoagulants. A complete resolution of symptoms and radiological alterations were observed within 7 weeks. In conclusion, lateral sinus thrombosis and Gradenigo's syndrome are rare but potential fatal complications of otitis media and mastoiditis. High-dose intravenous antibiotics and a low dose of anticoagulant can achieve a complete recovery without surgery.     

Recurrent cerebrovascular accident with L-asparaginase rechallenge

We report a 15-year-old boy diagnosed with acute lymphoblastic leukemia (ALL) in 1983. Induction therapy included L-asparaginase. After the second dose of L-asparaginase, he had a left sided focal seizure and computed tomography (CT) scan of the head showed a right frontal infarct. No further L-asparaginase was given. Complete remission was achieved and he successfully completed therapy in 1986. Eight months later he had an isolated bone marrow relapse. Reinduction therapy included L-asparaginase. After the fourth dose of L-asparaginase, he presented with severe headache and a CT scan showed a right temporal infarct. Repeat infarction on rechallenge with L-asparaginase has not been previously reported. Prophylactic therapy, such as fresh frozen plasma, should be considered before patients, with a previous cerebral insult, are rechallenged with L-asparaginase. However the effectiveness of such therapy has not been established. © 1992 Wiley-Liss, Inc.     

Cerebral venous sinus thrombosis: report of a case and review of the literature

Cerebral venous sinus thrombosis is a condition that is well documented as a complication of the latter stages of pregnancy and with an even greater incidence during the puerperium. More recently this entity had been associated with the use of oral contraceptives. A case is presented of a 15-year-old girl with this condition, in whom the occurrence as well as the resolution of a superior sagittal sinus thrombosis was demonstrated with serial computed tomography (CT) scans and radionuclide studies. The discussion of this case, coupled with a review of the literature, describes the clinical presentation, explores the possible etiology, offers a noninvasive technique for confirming the diagnosis, and presents the medical management of this condition. It is postulated that cerebral venous sinus thrombosis occurs with a greater frequency than is currently recognized. Health professionals involved with monitoring the health care of adolescents during pregnancy and in the puerperium should be aware of this potential complications. In addition, association of this condition with oral contraceptive use should be recognized.     

Recurrent cerebrovascular accident with L-asparaginase rechallenge.

We report a 15-year-old boy diagnosed with acute lymphoblastic leukemia (ALL) in 1983. Induction therapy included L-asparaginase. After the second dose of L-asparaginase, he had a left sided focal seizure and computed tomography (CT) scan of the head showed a right frontal infarct. No further L-asparaginase was given. Complete remission was achieved and he successfully completed therapy in 1986. Eight months later he had an isolated bone marrow relapse. Reinduction therapy included L-asparaginase. After the fourth dose of L-asparaginase, he presented with severe headache and a CT scan showed a right temporal infarct. Repeat infarction on rechallenge with L-asparaginase has not been previously reported. Prophylactic therapy, such as fresh frozen plasma, should be considered before patients, with a previous cerebral insult, are rechallenged with L-asparaginase. However the effectiveness of such therapy has not been established.     

Heparin induced thrombocytopenia and re‐thrombosis associated with warfarin and fondaparinux in a child

An 11‐year‐old female developed heparin induced thrombocytopenia (HIT) with thrombosis during therapy for lower extremity deep vein thrombosis and pulmonary embolism. Transition from bivalirudin, a direct thrombin inhibitor (DTI), to warfarin resulted in extensive re‐thrombosis, and fondaparinux therapy similarly failed. She was then treated with argatroban, and transitioned successfully to warfarin after 9 weeks. The risk of re‐thrombosis was ultimately reduced by allowing time for the thrombogenic potential to abate. The argatroban/warfarin transition was monitored with chromogenic factor X levels. This case highlights several difficult problems in pediatric thrombosis. Pediatr Blood Cancer 2009;53:468–471. © 2009 Wiley‐Liss, Inc.