Nowadays, cranial radiotherapy (RT), is still one of the mainstays treatments for brain tumour patients. Despite the poor prognosis of this population, some patients will achieve long-term overall survival. These include patients with low-grade or even high-grade primary brain tumours and patients with brain metastases with favorable clinical and molecular prognostic factors.
Yet, 50–90% of them will experience long-term cognitive deficits induced by cranial RT, thus impairing functional independence and quality of life [1–8]. Radiation-induced cognitive impairment is mainly characterized by deficits focused on attention, verbal and visual memory, visuospatial skills, and executive functions, which may be often disabling and permanent [9–12].
Typically, it has been considered that RT-induced neurotoxicity must be caused by direct damage to neurons or glia or by disruption of the normal cerebral vasculature [13]. Radiologically, it is observed as cerebral atrophy, white matter (WM) damage and ventricular dilatation [12–17]. The mechanisms of ventricular dilatation due to cranial RT are unknown. One of the postulated hypotheses is that cranial RT might induce the production of transforming growth factor β (TGF-β) leading to arachnoid granulation fibrosis and decreasing cerebrospinal fluid (CSF) drainage [17–19]. Often, ventricular dilatation is disproportionate to the cerebral atrophy, and it manifests clinically like normal pressure hydrocephalus (NPH): insidiously progressive gait disturbance, urinary incontinence, and cognitive impairment.
Thiessen and DeAngelis in 1998 performed a retrospective review of the potential benefit of ventriculoperitoneal shunting (VPS) in patients with RT-induced leukoencephalopathy (n = 30), showing that more than half of their patients obtained a favorable functional response after VPS, although only urinary incontinence achieved a statistically significant difference. Cognitive impairment showed minimal improvement, but importantly, only one third received formal neuropsychological testing [16]. Since then, only a few short series of patients or isolated clinical cases have been reported concerning hydrocephalus following cranial RT, and the potential benefit of VPS, resulting in no consensus on its diagnosis and management [17, 20, 21].
In the absence of standard criteria for NPH, the combination of clinical and neuroimaging features, such are Evans’ Index (EI) and disproportionate enlarged subarachnoid space hydrocephalus (DESH) are relevant to support diagnoses [22–24]. Although of great importance, due to its high false-negative associated rates, CSF Tap Test or CSF drainage test and lumbar infusion tests (LIT) are only used to support diagnosis when there is a high clinical suspicion and no typical MRI features are found [23]. Despite these assertions have been widely established in idiopathic NPH, there is still no clinical guidelines for secondary NPH. Secondary NPH, like post-RT NPH, encompasses a diverse group of acquired hydrocephalus, being the most common subarachnoid hemorrhage and traumatic brain injury. Interestingly, differences in outcome between idiopathic and secondary NPH have been observed, with substantial better outcome for secondary than for idiopathic NPH following VPS [25–27].
In this setting, identifying those cancer survivors with RT-induced cognitive impairment and NPH who may benefit from VPS becomes crucial. While some predictors of VPS responsiveness including the presence of DESH or a positive Tap Test has been described in idiopathic NPH, up to the best of our knowledge, nonreliable predictor of successful outcome for shunting has been associated to secondary NPH.
Our study examines cognitive deficits, as well as neuroimaging and infusion test features, in a series of patients who have a previous history of cranial RT and progressive cognitive decline together with urinary incontinence and/or gait disturbance, in which post-RT NPH is suspected. The aim of our study is to identify the clinical, neuroimaging and infusion test characteristics of those patients with post-RT NPH who may benefit from VPS.