|Year : 2021 | Volume
| Issue : 3 | Page : 190-195
Secondary intracranial hypertension in aplastic anemia: A case report and review of current concepts
Adil Al-Musalami1, Alaa Elmanzalawy2, Yasser Wali3, Anuradha Ganesh4
1 Ophthalmology Program, Oman Medical Specialty Board, Muscat, Oman
2 Department of Radiology, Sultan Qaboos University Hospital, Muscat, Oman
3 Department of Pediatric Hematology, Sultan Qaboos University Hospital, Muscat, Oman
4 Department of Ophthalmology, Sultan Qaboos University Hospital, Muscat, Oman
|Date of Submission||13-Mar-2021|
|Date of Decision||06-May-2021|
|Date of Acceptance||06-May-2021|
|Date of Web Publication||20-Oct-2021|
Dr. Adil Al-Musalami
R5, Ophthalmology Resident, OMSB
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Intracranial hypertension (IH) when detected mandates prompt and appropriate therapy to avoid permanent visual impairment. We report a 7-year-old boy who presented to the emergency services with purpuric rashes and bruises. Peripheral blood smear and bone marrow aspiration confirmed the diagnosis of aplastic anemia. During admission, the child developed headache, nausea, vomiting, and diplopia. Ophthalmic examination revealed intermittent esotropia and bilateral papilledema. The findings on neuroimaging and lumbar puncture led to the diagnosis of secondary IH (SIH). The intracranial pressure normalized on treatment with oral acetazolamide, oral furosemide, and intravenous dexamethasone.
Keywords: Aplastic anemia, idiopathic intracranial hypertension, intracranial hypertension, papilledema, secondary intracranial hypertension
|How to cite this article:|
Al-Musalami A, Elmanzalawy A, Wali Y, Ganesh A. Secondary intracranial hypertension in aplastic anemia: A case report and review of current concepts. Oman J Ophthalmol 2021;14:190-5
|How to cite this URL:|
Al-Musalami A, Elmanzalawy A, Wali Y, Ganesh A. Secondary intracranial hypertension in aplastic anemia: A case report and review of current concepts. Oman J Ophthalmol [serial online] 2021 [cited 2022 May 16];14:190-5. Available from: https://www.ojoonline.org/text.asp?2021/14/3/190/328614
| Introduction|| |
Intracranial hypertension (IH) can lead to permanent visual impairment. Primary IH, now known as idiopathic IH (IIH), occurs in the absence of any identifiable etiology, while secondary IH (SIH) is associated with an identifiable cause., Pediatric patients with IH are more likely to have associated systemic conditions than adults [Table 1]. The modified Dandy criteria are used for diagnosis of IIH and include (1) signs and symptoms of raised intracranial pressure (ICP) such as headache, nausea, vomiting, and papilledema; (2) no localizing signs on neurological examination (except for abducens nerve paresis); (3) cerebrospinal fluid (CSF) opening pressure of above 25 cm H2O with normal contents; and (4) radiographic signs of raised ICP but no structural cause or hydrocephalus.
IIH is a rare entity, and the annual pediatric incidence has been reported to vary from 0.47 to 1.2 per 100,000., The incidence of SIH is unknown. IIH in childhood has a greater incidence in adolescents (12–15 years) compared to young children (2–12 years). Adolescents with IIH have a clinical presentation which resembles that seen in adults. They present with headache, nausea, vomiting, transient visual obscurations, and diplopia. Female preponderance and an association with obesity are also noted. Gender predilection and obesity are uncommon in prepubertal children with IIH, and affected children are more likely to present with strabismus or stiff neck than headache or vomiting. Patients with SIH have similar physical symptoms and signs of raised ICP. Papilledema is a well-recognized sign and can be bilateral, unilateral, or asymmetric. Central visual acuity is usually preserved in the early stages. Impaired acuity at this stage usually reflects macular edema or exudates, optic nerve infarction, or subretinal hemorrhage.
SIH has been described in various anemias. A search in English literature revealed two reports of IH in the setting of idiopathic aplastic anemia., We report a child with idiopathic aplastic anemia and SIH, and present a review of current concepts in evaluation and management.
| Case Report|| |
A 7-year-old boy presented to the emergency services with purpuric rashes and bruises. Peripheral blood smear showed thrombocytopenia and neutropenia. No abnormal cells were seen. Bone marrow aspiration revealed markedly hypocellular bone marrow (5% cellularity) and no abnormal cells, leading to the diagnosis of aplastic anemia. He was referred to the pediatric ophthalmology service due to recent onset of headache, nausea, vomiting, and diplopia. Parents had noticed intermittent esodeviation. There was no history of transient visual obscurations or tinnitus.
Ophthalmic examination revealed visual acuity at 1.0 in both eyes (OU). Color vision (tested with Ishihara chart) was found to be normal OU. The pupils were normal in size and reaction to light. No relative afferent pupillary defect was noticed. Orthoptic evaluation showed an alternating intermittent esotropia of 18 prism diopters (PD) at near and 14 PD at distance. Extraocular muscle movements were normal. In particular, no abduction deficit was noted. Dilated fundus examination revealed bilateral disc swelling [Figure 1]. Cycloplegic refraction showed moderate hypermetropia of +6.0 D right eye (OD) and +5.75 D left eye (OS). Spectacle correction (full cycloplegic refraction) was advised. Humphrey visual showed enlarged blind spot OU [Figure 2]. Fundus fluorescein angiography was done and showed hyperfluorescence due to leakage, confirming the disc swelling to be due to papilledema [Figure 3]. Optical coherence tomography (OCT) showed increased average retinal nerve fiber layer (RNFL) thickness, normal macular contour, and macular ganglion cell layer (m-GCL) thickness [m-GCL; [Figure 4]].
|Figure 2: Humphrey visual field of both eyes, showing bilateral enlargement of blind spots|
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|Figure 3: Fundus fluorescein angiogram showing bilateral hyperfluorescence due to dye leakage confirming the disc swelling to be due to papilledema|
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|Figure 4: Optical coherence tomography optic disc: Retinal nerve fiber layer analysis of both eyes at presentation showing bilateral papilledema|
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Clinical examination by the pediatric neurologist was unremarkable. Magnetic resonance imaging (MRI) of the brain and orbits showed the absence of mass lesion and characteristic features of IH including prominent subarachnoid space around both optic nerves [Figure 5]. Magnetic resonance venogram (MRV) of the brain showed bilateral transverse sinus stenosis [Figure 6]. Lumbar puncture was performed and CSF opening pressure was found to be 50 cm H2O with normal CSF contents. The diagnosis of SIH was thus confirmed, and the child was started on oral acetazolamide (25 mg/kg/day – 250 mg, TID). Sodium bicarbonate 8.4% injection (35 ml) was added to combat metabolic acidosis. Intravenous dexamethasone (1 mg QID) and oral furosemide (7 mg TID) were added to aid resolution.
|Figure 5: Coronal and axial magnetic resonance imaging fat-suppressed T2-weighted magnetic resonance images of the brain and orbits showing mild prominence of the perioptic subarachnoid space (white arrows). There is mild tortuosity of the optic nerves. Bilateral flattening of the posterior eye globe is also noted (black arrows)|
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|Figure 6: Oblique coronal maximum intensity projection three-dimensional magnetic resonance venogram image of the brain showing bilateral stenosed lateral segments of the transverse sinuses (arrows). No evidence of venous thrombosis was seen on the contrast-enhanced magnetic resonance venogram|
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Follow-up after 5 weeks showed good response to the above treatment with resolution of headache, vomiting, and diplopia. Ophthalmic examination showed orthotropia with full stereopsis with glasses and flat optic discs [Figure 7]a. OCT showed a marked reduction in the RNFL thickness and preserved m-GCL [Figure 7]b. Bone marrow transplantation (BMT) was performed from a fully matched sibling. The post-BMT follow-up was uneventful for over 6 months.
|Figure 7: Five weeks after initial presentation, (a) fundus photo and (b) optical coherence tomography showed marked resolution of disc swelling|
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| Discussion|| |
We report a young boy with aplastic anemia who developed headache with vomiting during admission for management of his systemic condition. Papilledema was detected on ophthalmic evaluation. CSF opening pressure, MRI, and MRV findings were consistent with a diagnosis of IIH. The symptoms and signs did not resolve with oral acetazolamide alone. Resolution was achieved with addition of intravenous dexamethasone and oral furosemide.
Children often have SIH with underlying systemic conditions, and a careful history must be taken to exclude these., Various anemias including iron-deficiency anemia and hemolytic anemia have been reported in association with IH. It has been suggested that raised ICP in anemia may result from anemia-induced cerebral hypoxia. There is limited literature on IH in aplastic anemia. Lilley et al. reported IH in an 8-year-old girl with aplastic anemia. Like our patient, she had hyperopia and accommodative esotropia. However, lumbar puncture was not performed. She had full visual fields and the disc swelling subsided with resolution of the anemia. Nazir and Siatkowski reported a 13-year-old boy with idiopathic aplastic anemia. Magnetic resonance venography was normal. Although CSF opening pressure was 13.2 cm H2O initially, it was 53 cm H2O during the second lumber puncture. The raised ICP in this patient resolved on treatment with acetazolamide correction of the aplastic anemia with multiple blood transfusions and antithymocyte globulin.
OCT and fundus fluorescein angiography are useful tools to differentiate optic disc edema caused by papilledema or other optic neuropathies from optic disc elevation caused by optic nerve head drusen. Increased RNFL thickness is seen in disc edema and disc drusen. The presence of a smooth internal contour and a recumbent “lazy V pattern” of the subretinal hyporeflective space (SHYPS) is indicative of optic disc edema as opposed to the “lumpy-bumpy” internal contour with an abrupt decline in the SHYPS in optic disc drusen. The OCT pattern in our patient was consistent with clinical diagnosis of optic disc edema. Fluorescein angiography findings of profound leakage at the disc were confirmatory.
MRI is the preferred imaging technique in pediatric IIH and can help establish diagnosis by ruling out mass lesions and hydrocephalus. Nonlocalizing signs such as flattening of posterior sclera, distension of perioptic subarachnoid space, intraocular protrusion of the optic nerve, vertical tortuosity of the optic nerve, transverse sinus stenosis, and empty sella are pathognomonic of IIH. All these findings except empty sella were seen on neuroimaging in our patient.
Physicians may choose to defer performing a lumbar puncture in the setting of aplastic anemia due to the risks posed by prevailing thrombocytopenia and immunocompromised state. However, disc swelling may be seen in the setting of ischemia, infiltration, or inflammation. If neuroimaging rules out an intracranial space-occupying lesion, then lumbar puncture can be performed safely to document raised CSF pressure and normal CSF contents, establishing the diagnosis of IH.
The IIH Treatment Trial, a multicenter, randomized, double-masked, placebo-controlled study of acetazolamide in adult IIH patients with mild visual loss, demonstrated improvements in visual field function, and papilledema with treatment. Acetazolamide at a dose of 25 mg/kg/day in one to four divided doses up to a maximum dose of 100 mg/kg/day is used as a first-line treatment in pediatric IIH. In patients who do not respond to acetazolamide, loop diuretics, such as furosemide, can be used as adjunct therapy. A short course of steroids may be used in patients with papilledema and visual compromise. Our child required multiple lines of management. Repeated ophthalmic assessments ensured preserved optic nerve integrity.
In conclusion, IH in aplastic anemia is uncommon. Physicians managing aplastic anemia should be aware of this vision-threatening association. Adopting a low threshold to refer children with symptoms of IH for ophthalmic examination, prompt diagnosis, and appropriate management is essential to ensure an optimal outcome.
We would like to thank Iman Al Harthy, Ophthalmic technician, Department of Ophthalmology, Sultan Qaboos University Hospital, Muscat, Oman.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gordon K. Pediatric pseudotumor cerebri: Descriptive epidemiology. Can J Neurol Sci 1997;24:219-21.
Aylward SC, Reem RE. Pediatric intracranial hypertension. Pediatr Neurol 2017;66:32-43.
Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology 2013;81:1159-65.
Avery RA, Shah SS, Licht DJ, Seiden JA, Huh JW, Boswinkel J, et al.
Reference range for cerebrospinal fluid opening pressure in children. N Engl J Med 2010;363:891-3.
Rangwala LM, Liu GT. Pediatric idiopathic intracranial hypertension. Surv Ophthalmol 2007;52:597-617.
Cinciripini GS, Donahue S, Borchert MS. Idiopathic intracranial hypertension in prepubertal pediatric patients: Characteristics, treatment, and outcome. Am J Ophthalmol 1999;127:178-82.
Al-Senawi R, Ganesh A, Al-Busaidi A, Friedman, et al
. This is Ref 7. Al-Senawi R, Ganesh A, Al-Busaidi A, Al-Futaisi A, Al-Habsi N, Al-Zuhaibi S. Visual loss at presentation in children with pseudotumor cerebri. Oman J Ophthalmol [serial online] 2008 [cited 2021 Oct 2];1:18-24. Available from: https://www.ojoonline.org/text.asp?2008/1/1/18/43316
Lilley ER, Bruggers CS, Pollock SC. Papilledema in a patient with aplastic anemia. Arch Ophthalmol 1990;108:1674-5.
Nazir SA, Siatkowski RM. Pseudotumor cerebri in idiopathic aplastic anemia. J AAPOS 2003;7:71-4.
Knizley H Jr., Noyes WD. Iron deficiency anemia, papilledema, thrombocytosis, and transient hemiparesis. Arch Intern Med 1972;129:483-6.
Belman AL, Roque CT, Ancona R, Anand AK, Davis RP. Cerebral venous thrombosis in a child with iron deficiency anemia and thrombocytosis. Stroke 1990;21:488-93.
Lubeck MJ. Papilledema caused by iron-deficiency anemia. Trans Am Acad Ophthalmol Otolaryngol 1959;63:306-10.
Savini G, Bellusci C, Carbonelli M, Zanini M, Carelli V, Sadun AA, et al.
Detection and quantification of retinal nerve fiber layer thickness in optic disc edema using stratus OCT. Arch Ophthalmol 2006;124:1111-7.
Degnan AJ, Levy LM. Pseudotumor cerebri: Brief review of clinical syndrome and imaging findings. AJNR Am J Neuroradiol 2011;32:1986-93.
NORDIC Idiopathic Intracranial Hypertension Study Group Writing Committee, Wall M, McDermott MP, Kieburtz KD, Corbett JJ, Feldon SE, et al.
Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: The idiopathic intracranial hypertension treatment trial. JAMA 2014;311:1641-51.
Warman R. Management of pseudotumor cerebri in children. Int Paediatr 2000;15:147-50.
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