Letter to the Editor: Clinical experience
Two children with steroid-responsive nephrotic syndrome complicated by cerebral venous sinus thrombosis
Dos niños con síndrome nefrótico sensible a corticoides complicado por trombosis de seno venoso cerebral
Eda Didem Kurt-Şüküra,
, Zeynep Birsin Özçakara, Suat Fitözb, Songül Yilmaza, Serap Teberc, Elif Ünal İnced, Mesiha Ekima, Fatoş Yalçinkayaa
Corresponding author
a Division of Pediatric Nephrology, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey
b Department of Radiology, Ankara University School of Medicine, Ankara, Turkey
c Division of Pediatric Neurology, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey
d Division of Pediatric Hematology, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey
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array:3 [ "entidad" => "Division of Pediatric Nephrology, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Radiology, Ankara University School of Medicine, Ankara, Turkey" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Division of Pediatric Neurology, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Division of Pediatric Hematology, Department of Pediatrics, Ankara University School of Medicine, Ankara, Turkey" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Dos niños con síndrome nefrótico sensible a corticoides complicado por trombosis de seno venoso cerebral" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1739 "Ancho" => 1500 "Tamanyo" => 276149 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cranial MR on admission; superior sagittal sinus (A) and right transverse sinus (B) thrombosis (arrows). Follow-up MR angiography (C, D); sinuses are partially recanalized with persistant hypointense thrombotic filling defects (arrows).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Nephrotic syndrome (NS) is a common disorder of childhood. The risk of thromboembolic (TE) phenomena in children with NS is estimated as 1.8–5% with a higher incidence in steroid resistant forms.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Venous thrombosis is the most frequent type of thrombosis in childhood NS and occurs mainly in the deep venous system.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> Kerlin et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> reported 39 TE events among 326 NS patients and 29 of them were deep venous thromboses majority of which were seen in lower extremities. Although infrequent other sites like the cerebral venous system may also be affected and this presentation carries increased morbidity and mortality. Herein we present two children with minimal change disease (MCD) who experienced thrombosis of the cerebral sinovenous system.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Patient 1</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 15-year-old boy was admitted to our clinic with edema and 10<span class="elsevierStyleHsp" style=""></span>kg weight gain in a month. Physical examination (PE) showed generalized edema and ascites. Urinary examination showed 246<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/h proteinuria. Serum albumin level was 0.8<span class="elsevierStyleHsp" style=""></span>g/dl, cholesterol and triglyceride levels were 375<span class="elsevierStyleHsp" style=""></span>mg/dl and 190<span class="elsevierStyleHsp" style=""></span>mg/dl respectively. Hemoglobin (Hb) level was 16.2<span class="elsevierStyleHsp" style=""></span>g/dl. Renal biopsy was compatible with MCD. He was put on 60<span class="elsevierStyleHsp" style=""></span>mg/day prednisone treatment and remission was achieved on the 22nd day. Steroid was used as 60<span class="elsevierStyleHsp" style=""></span>mg/day for a month and tapered over 3 months. The day after cessation of prednisone generalized edema, headache and vomiting started. Laboratory investigations showed severe proteinuria, 1060<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/h and a serum albumin of 0.8<span class="elsevierStyleHsp" style=""></span>g/dl. His Hb level was 21.6<span class="elsevierStyleHsp" style=""></span>g/dl and hematocrit (htc) 63.8%. He was put back on 60<span class="elsevierStyleHsp" style=""></span>mg/day prednisone and intravenous fluid, albumin replacement, acetylsalicylic acid therapy were started. Cranial computed tomography (CT) was normal. Next day PE revealed lateral gaze palsy of the right eye. Cranial magnetic resonance imaging (MRI) and MR venography (MRV) were performed which showed subacute superior sagittal, right sigmoid and transverse sinus thromboses (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and B). Immediate anticoagulation with heparin was started. Investigations for inherited thrombotic risk factors were negative. On the third day of admission lateral gaze became normal. Two weeks later a repeat MRV showed partial recanalization of the thrombi (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C and D). Remission of NS was achieved on the 35th day of steroid treatment, then the dose was decreased and the patient was put on cyclosporine. He had complete neurological recovery and did not experience recurrence of NS or thrombosis during the two-year follow-up.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Patient 2</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 2.5-year-old boy with no significant past medical history presented to our clinic with puffiness of the eyelids, edema of legs and decreased urine output. He had gained 2<span class="elsevierStyleHsp" style=""></span>kg of weight in a week time. Physical examination revealed facial and pitting edema on extremities in addition to abdominal distension. Laboratory investigations showed Hb 14.9<span class="elsevierStyleHsp" style=""></span>g/dl, htc 45.9%, platelet count 406,000/μL, total protein 3.7<span class="elsevierStyleHsp" style=""></span>g/dl, albumin 1.4<span class="elsevierStyleHsp" style=""></span>g/dl, serum cholesterol 382<span class="elsevierStyleHsp" style=""></span>mg/dl and normal renal function tests. Urinary examination revealed heavy proteinuria; 244<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>/h. Serum C3 and C4 levels were normal. Nephrotic syndrome was diagnosed and the patient was put on 2<span class="elsevierStyleHsp" style=""></span>mg/kg prednisone treatment. On the 4th day of treatment the patient complained of headache. Cranial CT was normal. On the 5th day he developed right 6th cranial nerve palsy. Magnetic resonance imaging and MRV showed thromboses in the superior sagittal, right transverse and sigmoid sinuses extending into the jugular system (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Intravenous hydration, low molecular weight heparin (LMWH) were started immediately. Screening for inherited thrombophilias was negative. On 10th day patient's headache subsided, focal neurological signs resolved. Remission was achieved on the 14th day of steroid treatment. The patient was discharged on steroid and LMWH. He had complete neurological recovery and has not experienced any complication during follow-up for 6 months.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Cerebral sinovenous thrombosis is a rare but serious complication of NS with few isolated reports in the literature. Its incidence in children has been reported as 0.67/100.000 by the Canadian registry.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> The most frequent site reported for thrombus in CSVT patients is the superior sagittal sinus followed by the straight and the transverse sinuses.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> Appropriate imaging is necessary for timely diagnosis. In daily practice cranial CT is usually the preferred modality; however, it may miss CSVT in nearly 40% of patients.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> Magnetic resonance imaging with MRV is considered as the best method for the diagnosis and follow-up of pediatric CSVT.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The hypercoagulable state in NS is due to several potential mechanisms; urinary loss of anticoagulant proteins, especially antithrombin (AT) III, increased procoagulatory activity, increased platelet aggregation and thrombocytosis.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a> Hyperlipidemia may also be an additive factor.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Other factors include hemoconcentration, diuretic use, severe hypoalbuminemia and indwelling catheters. Thrombosis in NS is mainly a secondary phenomenon but all children should be checked for hereditary thrombotic disorders. Our patients had no family history for TE events and thrombophilia panel testing was negative in both. Kerlin et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> recently reported TE events in 6.6% of patients with primary NS and showed severity of proteinuria, adolescent age (>12 years), and history of TE disease correlate well with TE risk. Our patients had MCD with heavy proteinuria and very low serum albumin levels during the attack. Hemoconcentration was a striking finding in one of our patients. The first patient was an adolescent; however, the second case was a 2.5-year-old boy. Thromboembolic complications are known to be more prevalent early in the disease course.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> A median time of 70.8 days from NS diagnosis to the first TE is recently reported in concordance with previous reports, 61% of the events occurring in the first 3 months just as in our patients.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In the absence of major intracranial hemorrhage anticoagulation therapy is the preferred treatment in children with CSVT.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a> There is no current consensus over the prophylactic use of anticoagulation and in daily practice it is not used unless patient has a thrombosis history.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Our cases highlight the importance of clinical suspicion and early diagnosis in NS patients with any neurological symptom. Careful physical examination, appropriate imaging, acute anticoagulation and proper treatment of the NS would reduce morbidity and prevent life threatening complications.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Patient 1" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Patient 2" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1739 "Ancho" => 1500 "Tamanyo" => 276149 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cranial MR on admission; superior sagittal sinus (A) and right transverse sinus (B) thrombosis (arrows). Follow-up MR angiography (C, D); sinuses are partially recanalized with persistant hypointense thrombotic filling defects (arrows).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1739 "Ancho" => 1500 "Tamanyo" => 247811 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Coronal T2-weighted (A) and transverse T1-weighted (B) MR images show hyperintense thrombus in transverse and sigmoid sinuses (arrows). Contrast-enhanced MR angiography axial (C) and sagittal (D) reformatted images demonstrate thrombus as hypointense filling defects in right transverse sinus (curved-arrows).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemostatic problems and thromboembolic complications in nephrotic children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Citak" 1 => "S. Emre" 2 => "A. Sairin" 3 => "I. Bilge" 4 => "A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 7 | 11 |
| 2024 October | 45 | 35 | 80 |
| 2024 September | 33 | 19 | 52 |
| 2024 August | 60 | 48 | 108 |
| 2024 July | 35 | 26 | 61 |
| 2024 June | 43 | 41 | 84 |
| 2024 May | 59 | 33 | 92 |
| 2024 April | 63 | 38 | 101 |
| 2024 March | 60 | 19 | 79 |
| 2024 February | 56 | 48 | 104 |
| 2024 January | 36 | 22 | 58 |
| 2023 December | 36 | 24 | 60 |
| 2023 November | 59 | 28 | 87 |
| 2023 October | 49 | 27 | 76 |
| 2023 September | 43 | 23 | 66 |
| 2023 August | 54 | 27 | 81 |
| 2023 July | 87 | 18 | 105 |
| 2023 June | 59 | 21 | 80 |
| 2023 May | 76 | 30 | 106 |
| 2023 April | 55 | 15 | 70 |
| 2023 March | 59 | 21 | 80 |
| 2023 February | 45 | 15 | 60 |
| 2023 January | 46 | 26 | 72 |
| 2022 December | 61 | 26 | 87 |
| 2022 November | 64 | 26 | 90 |
| 2022 October | 99 | 35 | 134 |
| 2022 September | 57 | 21 | 78 |
| 2022 August | 50 | 47 | 97 |
| 2022 July | 51 | 42 | 93 |
| 2022 June | 52 | 38 | 90 |
| 2022 May | 61 | 28 | 89 |
| 2022 April | 50 | 47 | 97 |
| 2022 March | 44 | 41 | 85 |
| 2022 February | 69 | 38 | 107 |
| 2022 January | 80 | 30 | 110 |
| 2021 December | 74 | 37 | 111 |
| 2021 November | 50 | 33 | 83 |
| 2021 October | 67 | 44 | 111 |
| 2021 September | 48 | 36 | 84 |
| 2021 August | 52 | 34 | 86 |
| 2021 July | 54 | 30 | 84 |
| 2021 June | 62 | 23 | 85 |
| 2021 May | 55 | 34 | 89 |
| 2021 April | 95 | 51 | 146 |
| 2021 March | 57 | 30 | 87 |
| 2021 February | 47 | 21 | 68 |
| 2021 January | 51 | 14 | 65 |
| 2020 December | 35 | 16 | 51 |
| 2020 November | 42 | 16 | 58 |
| 2020 October | 41 | 26 | 67 |
| 2020 September | 43 | 14 | 57 |
| 2020 August | 39 | 11 | 50 |
| 2020 July | 56 | 11 | 67 |
| 2020 June | 51 | 12 | 63 |
| 2020 May | 45 | 12 | 57 |
| 2020 April | 36 | 17 | 53 |
| 2020 March | 44 | 19 | 63 |
| 2020 February | 57 | 19 | 76 |
| 2020 January | 66 | 28 | 94 |
| 2019 December | 64 | 24 | 88 |
| 2019 November | 39 | 19 | 58 |
| 2019 October | 41 | 11 | 52 |
| 2019 September | 44 | 19 | 63 |
| 2019 August | 38 | 18 | 56 |
| 2019 July | 40 | 21 | 61 |
| 2019 June | 34 | 19 | 53 |
| 2019 May | 46 | 32 | 78 |
| 2019 April | 96 | 37 | 133 |
| 2019 March | 38 | 18 | 56 |
| 2019 February | 32 | 16 | 48 |
| 2019 January | 28 | 16 | 44 |
| 2018 December | 212 | 38 | 250 |
| 2018 November | 342 | 17 | 359 |
| 2018 October | 363 | 16 | 379 |
| 2018 September | 139 | 17 | 156 |
| 2018 August | 95 | 21 | 116 |
| 2018 July | 93 | 16 | 109 |
| 2018 June | 110 | 14 | 124 |
| 2018 May | 116 | 13 | 129 |
| 2018 April | 157 | 11 | 168 |
| 2018 March | 134 | 13 | 147 |
| 2018 February | 95 | 5 | 100 |
| 2018 January | 71 | 5 | 76 |
| 2017 December | 72 | 6 | 78 |
| 2017 November | 56 | 13 | 69 |
| 2017 October | 36 | 8 | 44 |
| 2017 September | 31 | 14 | 45 |
| 2017 August | 39 | 7 | 46 |
| 2017 July | 31 | 9 | 40 |
| 2017 June | 39 | 7 | 46 |
| 2017 May | 59 | 7 | 66 |
| 2017 April | 42 | 16 | 58 |
| 2017 March | 35 | 6 | 41 |
| 2017 February | 112 | 10 | 122 |
| 2017 January | 30 | 13 | 43 |
| 2016 December | 41 | 11 | 52 |
| 2016 November | 62 | 16 | 78 |
| 2016 October | 80 | 10 | 90 |
| 2016 September | 148 | 1 | 149 |
| 2016 August | 72 | 3 | 75 |
| 2016 July | 127 | 3 | 130 |
| 2016 June | 73 | 0 | 73 |
| 2016 May | 104 | 0 | 104 |
| 2016 April | 99 | 0 | 99 |
| 2016 March | 71 | 0 | 71 |
| 2016 February | 91 | 0 | 91 |
| 2016 January | 68 | 0 | 68 |
| 2015 December | 38 | 0 | 38 |
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