This is a long-term follow-up multifarious study that has included patients with various HSCT types, different initial diagnoses, and different conditioning regimens. Similar studies that discussed CNS complications post-HSCT in both allogenic and autologous HSCT patients are scarce.
Sakellari et al. [8] reported an incidence of post-AlloSCT neurological complications ranging from 2.4 to 56%. The reported incidence of neurological complications varies greatly among the different centers due to different factors including the type of transplant, patient population, the definition of neurological complications, duration of follow-up, and study design.
It also varies according to the time the study was conducted, where in the last decades, the increase in the number of patients undergoing transplantation and progression of their overall survival make it more likely to develop unusual complications, such as neurological disorders [8].
In this study, post-AlloSCT CNS complications are more common than those of post-AuSCT; the incidence of post-AlloSCT and post-AuSCT CNSC are 39% and 11%, respectively. These results were, similar to those detected by Weber et al. [4].
Regarding post-allogenic HSCT, severe acute GVHD is an independent risk factor for the occurrence of CNSC (OR = 3.3, P value < 0.001); those results are in concordance with Nam Koh et al. [9] and Sakellari et al. [8] (OR = 11.96 P value < 0.001) [10].
The Chaudhary et al. [10] results regarding the female sex association with a higher likelihood to develop CNSC following AlloSCT were similar to our obtained results.
The most commonly observed CNSC in the current study was CNS disease recurrence (5%), followed by PRES (3.2%). However, Sakellari et al. [8] agreed that the most common post-HSCT CNSC is CNS recurrence with a much higher incidence (17%) than that detected in our study. Meanwhile, their reported PRES incidence was only 4%.
Recurrent malignancy is the leading cause of death in 14% of post-HSCT patients [11]. So, it is important to discriminate treatment-induced changes from pathology, post-transplantation lymphoproliferative disorder, and disease recurrence [12].
While this study results match those of Veljanovska et al.’s [13] regarding the incidence of PRES in AlloSCT patients (4.6%), Bhatt et al.’s [14] revealed a markedly higher incidence (40%). Cyclosporine was part of the GVHD prevention regimen of all post-AlloSCT patients in the study diagnosed with PRES. No correlation between supra-therapeutic calcineurin inhibitor levels, and PRES is noted.
During the follow-up, PRES was much more common at the < 100 day-post-HSCT period, during which 70.6% of PRES episodes occurred. These results are rather comparable to the findings of Veljanovska et al. [13] and Siegal et al. [15], which revealed that 86% of PRES episodes occurred during the first 100 days post-transplant.
MRI is still the gold standard in the diagnosis of PRES [16]. Bilateral symmetrical occipital affection was the most common imaging pattern. Atypical PRES sites are comparable to the findings of Chaudhary et al. [10], including the cerebellum, basal ganglia, and thalamus in 29.4, 11.4, and 6%, respectively.
The literature stated that the most common finding for PRES is a high signal on T2WI and FLAIR sequences. This supported the current study results where CT and T1WI MRI findings of our PRES patients were inconclusive, and the main distinctive features were the high T2 and FLAIR signals [13].
Diffusion restriction was detected in 29.4% of the diagnosed PRES patients, with no definite relation to the signal’s reversibility or residual neurological insult. The latest studies revealed that prediction of the outcome of PRES based on DWI (diffusion-weighted imaging) and ADC (apparent diffusion coefficient) values should be used with caution as diffusion restriction is no longer directly linked to PRES irreversibility and permeant neurological insult [16].
Emad-Eldin & Abdel-Moeti’s [17] study of 33 post-allogenic HSCT patients with CNS complications revealed a 15% incidence of leukoencephalopathy; our study including both allogenic and autologous HSCT patients (525) shows a prominently lower incidence of 1.9%; all of them had undergone AlloSCT, and all of them had methotrexate in their GVHD prophylaxis protocol.
Literature stated that in patients undergoing HSCT, clinically significant cerebral bleeding was more common than symptomatic thrombotic events where both are important causes of morbidity and mortality [18]. Similarly, our study revealed a higher incidence of post-HSCT hemorrhagic episodes (1.5%) compared with CVT (cerebral venous thrombosis) episodes (0.9%).
Compared with our study, Emad-Eldin & Abdel-Moeti [17] and Chaudhary et al. [10], revealed higher incidence of post-HSCT intracranial hemorrhage in 6 and 3.4%, respectively. Moreover, Gerber et al. [19], Emad-Eldin & Abdel-Moeti [17], and Hierlmeier et al. [1] reported higher incidences of CVT of 4.6, 3, and 12.2%, respectively.
AlloSCT patients were found to have a higher incidence of CVT and hemorrhagic episodes (1.4 and 2.8%, respectively) compared to AuSCT patients (0.6% each). Similarly, Hierlmeier et al. [1] and Labrador et al. [20] proved that AuSCT (versus AlloSCT) is protective for HSCT-related thrombocytopenia and CVT.
Maffini et al. [11] stated that subdural hematoma is the most common type of imaging-detected post-HSCT intracranial hemorrhagic episode. Similar results were detected in this study, where subdural hemorrhage was noted in 37.5% of hemorrhagic episodes.
For imaging assessment of post-HSCT CNS complications in pediatric patients, CT examination is to be avoided whenever possible due to radiation hazards and the fact that its main indication for hemorrhage detection can be superseded by susceptibility imaging. Limited MRI protocols distinctively tailored for each patient are often required to reduce patient under anesthesia time and risk of contrast administration. A proposed imaging protocol is illustrated in Fig. 7.
The limited number of patients in each subgroup of complications restrain proper assessment. Therefore, further studies with larger patient numbers are required for a deeper understanding of the pathogenesis, etiologic factors, risk factors for post-HSCT CNS complications. This may help to design preventive strategies and may refine treatment approaches.