Interplay between vascular hemodynamics and the glymphatic system in the pathogenesis of idiopathic normal pressure hydrocephalus, exploring novel neuroimaging diagnostics.

As the aging population continues to grow, so will the incidence of age-related conditions, including idiopathic normal pressure hydrocephalus (iNPH). The pathogenesis of iNPH remains elusive, and this is due in part to the poor characterization of cerebral spinal fluid (CSF) dynamics within the brain. Advancements in technology and imaging techniques have enabled new breakthroughs in understanding CSF physiology, and therefore iNPH pathogenesis. This includes understanding the hemodynamic and microvascular components involved in CSF influx and flow. Namely, the glymphatic system appears to be the great mediator, facilitating perivascular CSF flow via astrocytic aquaporin channels located along the endothelium of the pial vasculature. The interplay between glymphatics and both arterial pulsatilty and venous compliance has also been recently demonstrated. It appears then that CSF flow, and therefore glymphatic function, are highly dependent on cardiocirculatory and vascular factors. Impairment in any one component, whether it be related to arterial pulsatility, microvascular changes, reduced venous drainage, or astrogliosis, contributes greatly to iNPH, although it is likely a combination thereof. The strong interplay between vascular hemodynamics and CSF flow suggests perfusion imaging and cerebral blood flow quantification may be a useful diagnostic tool in characterizing iNPH. In addition, studies detecting glymphatic flow with magnetic resonance imaging have also emerged. These imaging tools may serve to both diagnose iNPH and help delineate it from other similarly presenting disease processes. With a better understanding of the vascular and glymphatic factors related to iNPH pathogenesis, physicians are better able to select the best candidates for treatment.

Early and Late Posttraumatic Epilepsy in the Setting of Traumatic Brain Injury: A Meta-analysis and Review of Antiepileptic Management.

BACKGROUND: Moderate to severe traumatic brain injury confers increased risk of posttraumatic seizures (PTSs). Early PTSs are diagnosed when seizures develop within 7 days after injury, whereas seizures diagnosed as late PTSs occur later. Patients have been treated with phenytoin (PHT) to prevent early PTSs and more recently with levetiracetam (LEV). Various regimens have been tried in patients to prevent late PTSs with variable success. We assessed and compared effectiveness of these drugs on early and late PTS prevention. METHODS: A literature search revealed 120 articles. Data were included if the same factors were compared across studies with identical treatment arms. Random effects models were used for meta-analysis to combine data into an overriding odds ratio (OR) comparing PTS incidence. For early PTSs, PHT was compared with placebo and LEV with PHT. For late PTSs, each drug was compared with placebo. RESULTS: Sixteen studies were included. PHT was associated with decreased odds of early seizures relative to placebo (OR = 0.34, 95% confidence interval [CI] 0.19-0.62). There was no difference in early seizure incidence between LEV and PHT (OR = 0.83, 95% CI 0.33-2.1). Neither LEV (OR = 0.69, 95% CI 0.24-1.96) nor PHT (OR = 0.4, 95% CI 0.1-1.6) was associated with fewer late PTSs than placebo. CONCLUSIONS: New literature is consistent with current guidelines supporting antiepileptic drug administration for prevention of early, but not late, PTSs. With regard to early PTS prevention, LEV and PHT are similarly efficacious, which is consistent with current guidelines. Side-effect profiles favor LEV administration over PHT.

An Examination of the Role of Supramaximal Resection of Temporal Lobe Glioblastoma Multiforme.

BACKGROUND: Resection of the T1 contrast-enhancing portion of glioblastoma multiforme (GBM) has been shown to increase patient survival, although whether GBM resection beyond these boundaries has an additional survival benefit is not clear. In this study, we examined the effect of resecting the enhancement and a margin of brain tissue surrounding the enhancement in patients with GBM of the temporal lobe. METHODS: We identified 32 consecutive patients with temporal lobe GBM who underwent initial resection between 2012 and 2015. Progression-free survival (PFS) and overall survival (OS) were analyzed based on the following categories: subtotal resection (STR; <99% of contrast enhancement removed), gross total resection (GTR; 100% of T1 contrast enhancement removed), and supramaximal resection (SMR; removal of T1 contrast enhancement plus removal of at least 1 cm of brain tissue surrounding the enhancement). RESULTS: Patients undergoing SMR demonstrated a substantially improved median PFS (15 months) compared with those undergoing GTR (7 months) or those undergoing STR (6 months) (P < 0.003). A median OS advantage was also present in the SMR group (24 months) compared with the GTR (11 months) and STR (9 months) groups (P < 0.004). SMR significantly improved PFS (hazard ratio [HR], 0.093; 95% confidence interval [CI], 0.01-0.89; P = 0.039) and OS (HR, 0.169; 95% CI, 0.05-0.57; P < 0.004) when controlling for other variables. The complication rates did not differ among the resection groups (P = 0.66). CONCLUSIONS: Achieving SMR substantially improved survival in patients with temporal lobe GBM compared with GTR of the enhancement alone.