Hydrocephalus is widely acknowledged as a potential complication of hemispherectomy surgery, yet there remains ambiguity regarding its underlying risk factors and mechanisms of onset. There is a scarcity of literature exploring this phenomenon in pediatric hemispherectomy patients previously treated for hydrocephalus, who are often excluded from hemispherectomy study cohorts in efforts to minimize confounding[17]. Though limited by a relatively small sample size (n = 19), this study provides insight into the factors associated with shunt malfunction following hemispherectomy in pediatric patients with pre-existing ventriculoperitoneal shunts.
The pathophysiological mechanisms leading to the onset of postoperative hydrocephalus remain unclear. Given the emerging risk factors associated with post-hemispherectomy hydrocephalus, it is important to consider the seminal findings within the past decade that are further clarifying our understanding of CSF production, flow, and absorptive patterns. The historical view of CSF generation and resorption posits that CSF is primarily produced by the choroid plexus lining the ventricles, flowing through the subarachnoid space, and eventually reabsorbed into the bloodstream through arachnoid granulations[19, 31],. However, recent findings call for a re-evaluation of this traditional narrative. Growing evidence suggests that fluid filtration across astrocytic podocytes – which comprise an important component of the blood brain barrier – may be a dominant source of CSF production[5, 11]. Furthermore, studies using animal models have uncovered that arachnoid granulations may not be the primary route by which CSF exits the brain; instead, CSF may be predominantly effluxing through olfactory epithelium – a finding which has major implications for the study of neurodegenerative disease[15, 24–25],.
Perhaps most relevant to the discussion of hydrocephalus is the discovery of a “glymphatic” network within the brain, by which interstitial fluid of the brain parenchyma is drained via peri-vascular pathways[10–11, 14, 20, 29]. The discovery of this glymphatic system, along with the incidental finding of lymphatic vessels embedded within dural infoldings adjacent to venous sinuses in the brain of mouse models, has revealed an alternate route of CSF efflux via deep cervical lymph nodes of the neck[3, 21–22]. In light of these new findings, it is conceivable that surgical disruption of the meningeal lymphatic network may play a significant role in the development of postoperative hydrocephalus.
At our institution, postoperative care routine has evolved over the last 25 years as performing hemispherectomy surgery has become a more prevalent treatment option for patients with drug resistant epilepsy. Most patients undergoing the procedure will have a ventricular catheter placed intra-operatively within the resection cavity. If they have a pre-existing shunt with an adjustable valve, the shunt will be turned to its highest setting or “off”, in order to reduce the flow of bloody or proteinaceous surgical debris through the shunt during the perioperative period. Fixed-valve shunts are left unchanged. The ventricular catheter is clamped in the 24 hours post-resection period to allow for reaccumulation of cerebrospinal fluid. A subgaleal drain is also placed at the time of surgery with suction turned on. The ventricular drain is opened to 10 mmHg above the tragus on post-operative day 1 and the subgaleal drain is taken off suction. On post-operative day 2, the subgaleal drain is removed and the ventricular drain is dropped until CSF drainage of 5–10 mL per hour is achieved. This is performed in order to remove blood and post-operative debris from the resection cavity and ventricles, possibly reducing the incidence of aseptic meningitis and shunt occlusion. The external ventricular drain (EVD) is typically removed between post-operative days 3–5, with the timing determined primarily by the color and quality of CSF output. The patient’s shunt is then returned to its original settings. Patients are managed in the Pediatric Intensive Care Unit until the ventricular drain is removed. While the EVD is in place, daily CSF samples are sent for routine culture analysis, collected directly from the distal collection column of the system by nursing staff, using sterile technique. Importantly, our findings herein suggest that use of post-operative EVD does not appear to be associated with any higher complication rate in hemispherectomy patients with pre-existing ventriculoperitoneal shunts.
26.3% of patients in this study required shunt revision due to shunt malfunction following hemispherectomy, with the median time to shunt failure as approximately five months. Our data supports that patients who experience shunt malfunction prior to hemispherectomy surgery are more likely to require postoperative shunt revision. The positive association between pre-hemispherectomy shunt revisions and post-hemispherectomy shunt revisions suggests that incidence of previous shunt revision surgery may be prognostic of poor postoperative shunt patency. Full interpretation of this trend is limited when considering that certain subpopulations of patients with pre-existing hydrocephalus have a greater underlying susceptibility to shunt malfunction throughout their lifetime, dependent on many different factors[7, 16].
Within our series, the time to first post-hemispherectomy shunt revision ranged from 2 days to 2.6 years, supporting existing consensus that hydrocephalus can occur relatively soon after surgery, or may take a more latent course of development[9, 17, 23, 27–28, 32],. Regarding patients who experienced shunt failure > 60 days postoperatively, it is possible that the hemispherectomy had little or no bearing on the episode of delayed shunt malfunction. Of the three patients presenting with delayed post-hemispherectomy hydrocephalus, one patient presented with symptoms of post-operative hydrocephalus requiring intervention 5 months postoperatively, while the other two patients required postoperative shunt revision 1.3 and 2.6 years post-hemispherectomy. It is conceivable that patients presenting with shunt failure within 1 year postoperatively are more likely to have hydrocephalus specifically attributed to the surgical intervention whereas those presenting with shunt failure years after surgery could be due to factors unrelated to the hemispherectomy procedure. Nonetheless, any neurosurgical procedure can lead to scarring and fibrosis of the region of interest, which may impede the normal drainage pathways of CSF, leading to a delayed-onset hydrocephalus[12]; this could explain the mechanism underlying delayed onset postoperative hydrocephalus. Still, the pathophysiological differences of early versus delayed onset postoperative hydrocephalus have yet to be discerned.
Etiology of hydrocephalus likely influences a patient’s propensity to develop shunt failure. In our sample, the etiology of hydrocephalus for the children who presented with postoperative shunt failure was congenital/idiopathic (n = 1) or due to perinatal vascular insult (n = 4). Existing literature implicates the etiology of hydrocephalus, particularly intraventricular hemorrhage and congenital defects, as potential risk factors for shunt failure[28, 33]. Patients with history of perinatal intracranial hemorrhage might exhibit a baseline pattern of proinflammatory expression causing ependymal damage, predisposing them to an increased risk for acquired postoperative hydrocephalus[8, 13]. This perspective provides a conceptual framework through which to interpret the positive association between frequency of preoperative shunt revisions and post-hemispherectomy shunt failure.
Other pertinent considerations regarding risk factors for shunt failure include shunt location and valve type. Previous investigations report conflicting findings on whether shunt approach affects shunt revision rates. In 2009, a prospective study performed by Farahmand et al. found that placement of proximal ventricular catheter in the right frontal lobe was associated with a lower rate of shunt revision within 6 months of insertion in adult patients with hydrocephalus[6]. Contrarily, in 2019, Bhargav et al. reported negligible difference in revision rates between frontal and parietal approaches for ventricular shunt placement in treatment of idiopathic normal pressure hydrocephalus[1]. Our study does not provide convincing evidence of a skewed distribution of shunt failure depending on location of the proximal catheter, given that there is a relatively balanced distribution of frontal (n = 2) and parieto-occipital (n = 3) proximal catheter placements for patients presenting with post-hemispherectomy shunt failure. In this study, two of five patients requiring post-hemispherectomy shunt revision had ipsilateral placement of proximal shunt catheter; one of five patients had contralateral placement; and two of five patients had bilateral shunts. At the traditional significance threshold of α = 0.05, our data shows a significant association linking ipsilateral location of the ventricular shunt catheter to a higher incidence of post-hemispherectomy shunt failure (p = 0.035); however, when the significance threshold is adjusted with Bonferroni correction to α = 0.00625, this statistical association is nullified (see Limitations). Additionally, of the patients in this sample who developed postoperative hydrocephalus, two had fixed pressure valves in place prior to hemispherectomy, and three had adjustable pressure valves. Whereas some studies suggest adjustable valves may lessen risk for shunt failure[6], others have found no association between valve programmability and shunt patency[30, 33]. Further investigation is needed in order to discern the true relationship between valve type and risk for postoperative hydrocephalus.
Meanwhile, our study reports no statistically significant association between post-hemispherectomy shunt failure and intraoperative shunt alteration; postoperative EVD usage; postoperative complication; or postoperative aseptic meningitis. This implies that postoperative management of pediatric hemispherectomy patients with pre-existing ventriculoperitoneal shunts should be dichotomized into consideration of (i) factors affecting acute perioperative care, and (ii) factors affecting longitudinal shunt patency.
Limitations
This study has several limitations. The retrospective design serves as an intrinsic constraint, primarily due to the nature of electronic medical record (EMR) data collection, which may be subject to recall bias, incomplete documentation, or changes in data collection practices over time. We attempted to mitigate analysis errors attributed to these factors by reviewing all note types in each patient’s EMR, repeating chart review for all patients three times, and cross-referencing extracted data amongst the authors responsible for data collection. Additionally, the generalizability of this study is confined by its small sample size. The limited number of hemispherectomy cases performed by any single epilepsy center has restricted the availability of data on risk factors for post-hemispherectomy complications. Nonetheless, the benefit conferred by case studies is the detail of patient data, which we seek to provide with transparency in order to add to the growing fund of literature exploring hydrocephalus as a postoperative sequela of hemispherectomy surgery (Online Resource 1: Supplemental Table).
Due to the small sample size, the statistical tests performed on our data may not have sufficient power to detect a statistically significant difference, even if a clinically meaningful difference exists. It is worth noting that an appreciable critique of the Bonferroni correction is that it is overly conservative; its use decreases risk of Type I errors, with a risk of increasing Type II errors and potentially missing valid significant findings[2]. Considering that the historical determination of the standard a = 0.05 has been set arbitrarily, it may be important to pay attention in clinical settings and future studies to variables nearing statistical significance before the Bonferroni adjustment – such as the number of pre-hemispherectomy shunt revisions, valve type, need for hemispherectomy revision surgery, or lateralization of proximal shunt catheter relative to resection. Ultimately, the conclusions to be drawn from the statistics reported in this case series should be interpreted within the context of existing literature exploring risk factors for postoperative hydrocephalus.
Relevance & Future Applications
The intent of this case series is to draw attention to certain clinical features in the past medical history that should be reviewed by neurosurgeons, neurologists, and other clinical team members when consulting families about postoperative expectations and risks following hemispherectomy in patients with pre-existing ventriculoperitoneal shunts. Frequency of shunt revisions prior to hemispherectomy may be indicative of a patient’s propensity to develop post-hemispherectomy hydrocephalus necessitating further shunt revision. A multicenter prospective study would be helpful to corroborate the findings of this case series and further distinguish risk factors for postoperative hydrocephalus in pediatric hemispherectomy patients with previously shunted hydrocephalus.