|Year : 2020 | Volume
| Issue : 4 | Page : 202-205
Pediatric transfusion-associated posterior reversible encephalopathy syndrome
Siddhant Lalwani1, Guruprasad Hassan Shankar1, Priscilla Joshi2, Bhakti Sarangi1
1 Department of Pediatrics, Bharati Vidyapeeth Medical College and Hospital, Pune, Maharashtra, India
2 Department of Radiodiagnosis, Bharati Vidyapeeth Medical College and Hospital, Pune, Maharashtra, India
|Date of Submission||11-Apr-2020|
|Date of Decision||13-May-2020|
|Date of Acceptance||17-May-2020|
|Date of Web Publication||13-Jul-2020|
Dr. Guruprasad Hassan Shankar
Department of Pediatrics, Bharati Vidyapeeth Medical College and Hospital, Pune - 411 043, Maharashtra
Source of Support: None, Conflict of Interest: None
Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome characterized by headache, altered mental state, seizures, and visual loss. It has a diverse etiology, of which hypertension is the most common. However, transfusion-associated PRES is being increasingly recognized, although pediatric reports are rare. We hereby report a 7-year-old boy with β thalassemia major, who developed neurological symptoms with changes suggestive of PRES on imaging after routine transfusions with an elevation of hemoglobin levels >5 g/dl posttransfusion. He required mechanical ventilation with standard therapies for raised intracranial pressure. The cerebral edema was characterized as vasogenic, due to the absence of diffusion restriction on magnetic resonance imaging of the brain and the child made a complete neurological recovery with normalization of imaging findings 4 weeks later. Interestingly, in concordance with the pressure, autoregulation disruption theory as a mechanism of hypertensive PRES, literature review on viscosity based autoregulation disruption shows that this may be one of the mechanisms among others for PRES associated with blood transfusion.
Keywords: Posterior reversible encephalopathy syndrome, transfusion, viscosity autoregulation
|How to cite this article:|
Lalwani S, Shankar GH, Joshi P, Sarangi B. Pediatric transfusion-associated posterior reversible encephalopathy syndrome. J Pediatr Crit Care 2020;7:202-5
|How to cite this URL:|
Lalwani S, Shankar GH, Joshi P, Sarangi B. Pediatric transfusion-associated posterior reversible encephalopathy syndrome. J Pediatr Crit Care [serial online] 2020 [cited 2020 Aug 9];7:202-5. Available from: http://www.jpcc.org.in/text.asp?2020/7/4/202/289523
| Introduction|| |
Posterior reversible encephalopathy syndrome (PRES) is an increasingly reported clinicoradiological syndrome of diverse etiologies, of which hypertensive encephalopathy and the use of immunosuppressant/cytotoxic drugs are more common. Characterized by a myriad of headache, altered mental state, seizures, and visual loss, PRES is typically seen to involve bilateral white matter in the posterior regions of both cerebral hemispheres, mostly affecting the occipital and parietal lobes. Although the pathogenesis remains unclear, the importance of disordered cerebral autoregulation and endothelial dysfunction is recognized. As the understanding of the condition evolves, it is recognized that radiological findings may also be present anteriorly and white matter involvement is not mandatory. Non-hypertensive and transfusion related unusual etiologies have now been commonly recognized and reported. The rare occurrence of irreversible neurological sequelae has also been established. We hereby report a 7-year-old male child with β-thalassemia major and transfusion-associated PRES.
| Case Report|| |
A 7-year-old boy, diagnosed with beta-thalassemia major at 6 months of age on regular packed cell volume (PCV) transfusions every 21 days and chelation therapy (total 65 transfusions from the time of diagnosis, median pre transfusion hemoglobin (Hb) 7.4 g/dl, oral deferasirox at 30 mg/kg/day, and last ferritin 5851 ng/ml) was transfused with 3 units of PCV (300 ml each) over 3 days on a Hb of 4.3 g/dl as part of routine transfusion therapy. A day after discharge, he was brought to the emergency department in status epilepticus of 2 h duration. At arrival, he was found to be in an actively convulsing state, with unresponsiveness, and deviation of the eyes to the right side. He had a heart rate of 170/min, bradypnea of 8 breaths/min, SPO2 of 60% on room air, and afebrile and blood pressure (BP) of 90/60 mmHg. He was started on the bag and mask ventilation and given 2 doses of IV lorazepam followed by loading doses of intravenous (IV) fosphenytoin and IV levetiracetam after which his seizures subsided. In view of continued poor respiratory efforts, with a Glasgow Coma Scale (GCS) of 5/15 postseizure control, he was intubated in the Emergency room (ER). He underwent emergency computed tomography (CT) of the brain in view of new-onset focal seizures in the background of beta-thalassemia major/acute febrile illness leading to a differential of stroke/central nervous system infection. CT of the brain revealed suspicious attenuation of the lateral ventricles; hence, a magnetic resonance imaging (MRI) of the brain was suggested and done in the same sitting. His MRI of the brain [Figure 1] and [Figure 2] showed symmetrical hyperintensities in the parietal lobes bilaterally on fluid-attenuated inversion recovery (FLAIR) images, not showing restricted diffusion suggestive of vasogenic edema. No corresponding signal abnormality on the diffusion-weighted imaging or apparent diffusion coefficient was present. A possibility of transfusion induced PRES was suggested in view of bilaterally symmetrical involvement of the parietal lobes posteriorly. Complete hemogram on admission [Table 1] showed a Hb of 13.9 g/dl with mild thrombocytopenia (80,000/cu mm), normal coagulation profile (prothrombin time-14.4 s, activated partial thromboplastin time-40 s, and international normalized ratio-1.2) with no biochemical abnormalities (serum electrolytes and renal functions tests) except hypoalbuminemia [Table 2]. Thrombocytopenia worsened on day 2 after which it improved spontaneously over a period of 6 days. In association with a febrile illness and negative C-reactive protein with no focus of infection, it was thought to be due to a viral illness. His cerebrospinal fluid (CSF) examination was also normal (total cells-01/cumm, sugars-75 mg/dl, and proteins-24 mg/dl). Dengue serology was sent, which was negative. During his pediatric intensive care unit stay, he remained normotensive (90–100/55–65 mmHg), and he was seizure-free through the rest of the hospital stay. He was given neuroprotective measures for 48 h, including hyperosmolar therapy with 3% saline. Sedation was relaxed after 48 h and GCS assessed, and found to be E4VTM6. He was hence extubated on day 3 of admission. His neurological examination postextubation was found to be normal. The illness gradually resolved over a week, and his blood and CSF cultures remained sterile. He was discharged without any neurological deficit, on oral antiepileptics. MRI of the brain done 4 weeks after the initial admission [Figure 3] was normal, thus corroborating a diagnosis of vasogenic edema due to PRES.
|Figure 1: A limited magnetic resonance imaging brain study revealed symmetrical fluid-attenuated inversion recovery hyperintensities in the parietal lobes posteriorly|
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|Figure 2: Diffusion weighted imaging shows no abnormal signal to suggest restricted diffusion|
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|Figure 3: Follow up magnetic resonance imaging brain after 4 weeks revealed regression of the previously seen signal abnormality on the fluid attenuated inversion recovery images|
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| Discussion|| |
PRES was first described in 1996 by Hinchey et al. The classic clinical presentation includes headache, altered sensorium (ranging from somnolence to stupor/coma), seizures, and visual disturbances with characteristic neuroimaging findings of bilateral white matter edema in posterior regions, most commonly parietal and occipital lobes.
Children are said to be more susceptible than adults to PRES due to the narrower range of autoregulation. Pediatric cases, however, are uncommon in literature but are possibly under-recognized. Mean age of presentation from pooled data (n = 127) from ten published pediatric series across different etiologies (hypertension, immunosuppression, and chemotherapy) was 11.6 years, with a 1:1 gender distribution,,,, in contrast to adults where it occurs predominantly in females.
The final pathophysiological pathway is thought to be disordered cerebral autoregulation and/or endothelial dysfunction., In hypertension-induced PRES, as the upper limit of pressure autoregulation is exceeded, arterioles dilate, and cerebral blood flow (CBF) increases passively to the pressure, causing hyperperfusion, breakdown of the bloodbrain barrier in arterial border zones, and vasogenic edema. Children are vulnerable to PRES at lower BPs than adults. Direct endothelial dysfunction has been implicated in PRES caused by cytotoxic therapies. With improved understanding of the condition, it is now well known that “PRES” may neither be confined to posterior regions nor be reversible. Diffusion restriction noted on MRI may alert the clinician to the presence of cytotoxic rather than vasogenic edema and portend a poorer prognosis with the possibility of neurologic sequelae.
PRES has also been described after blood transfusion. Neurological abnormalities resembling PRES were known to occur after blood transfusion in sickle cell disease. A literature review noted that the cause of anemia for which transfusions were given was varied, the course was chronic (71%), and anemia was severe in almost all of the assessable cases with an increase in Hb of at least 5 g/dl before the onset of PRES, with a mean onset of neurologic manifestations after transfusion being 1–18 days. Sixty-two percent of these cases were normotensive.
The differentials in this scenario could be an infectious/inflammatory process and PRES. However, though CSF may be normal in viral encephalitis, it is uncommon (3%–5%). The MRI findings in viral encephalitis are usually associated with restricted diffusion and rarely involve the parietal lobes. There were no clinical features including behavioral changes, cognitive impairment, movement disorders, especially suggestive of an autoimmune etiology, and MRI in autoimmune encephalitis more commonly shows changes in the temporal/limbic systems. The rapid neurologic recovery not in tandem with the course of the infection also suggested that the neurologic manifestations may not have been related to the febrile illness. The literature review does not suggest an association between thrombocytopenia and PRES. Hence, PRES was deemed more likely from the clinical presentation/course and progression of the illness as well as the imaging findings. The features of the present case were in accordance with many of the findings reported in the literature for transfusion-associated PRES in terms of severe chronic anemia with a rise in Hb level was >5 g/dl posttransfusion and presentation of symptoms 1 day later. There was no hypertension throughout hospital stay and CSF examination was normal. MRI of the brain showed symmetrical hyperintensities in the parietal lobes bilaterally on FLAIR images, not showing restricted diffusion suggestive of vasogenic edema. Hypoalbuminemia, as reported earlier, could have been a contributing factor. Finally, repeat MRI showing resolution in 4 weeks, consistent with vasogenic edema.
Several mechanisms have been proposed to explain PRES changes as a consequence of transfusion,, including cerebral vasoconstriction, abrupt vasospasm due to rapid correction of anemia, rapid increase in viscosity leading to endothelial dysfunction, and increase in blood volume, causing cerebral hyperperfusion. However, consistent with the breakdown of pressure autoregulation as in hypertension associated PRES, crossing the limits of viscosity-related autoregulation may be proposed as a pathophysiologic mechanism for transfusion-associated PRES.
Red blood cell transfusion has been demonstrated to result in a worsening of pressure reactivity index in severe traumatic brain injury patients, indicating impaired cerebral autoregulation. Physiologic studies in animals have revealed that viscosity changes must result in compensatory readjustments of vessel diameter (blood viscosity auto regulation of CBF), i.e., vasodilation has to occur with increased viscosity to maintain the same flow. Once autoregulation fails, there is a passive fall of blood flow despite increased viscosity leading to cerebral ischemia. Furthermore, viscosity has a greater role in the regulation of CBF when baseline CBF is increased, in conditions such as chronic anemia, where hypoxic cerebral vasodilation is occurring.
| Conclusion|| |
It is imperative for clinicians to be aware of transfusion-associated PRES while managing patients with chronic anemia of a severe degree with blood transfusions. Any new-onset neurologic deterioration in this context warrants investigation for PRES.
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.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]