Hydrocephalus is a common brain disorder that is treated only with surgery. The basis for surgical treatment rests on the circulation theory. However, clinical and experimental data to substantiate circulation theory have remained inconclusive. In brain tissue and in the ventricles, we see that osmotic gradients drive water diffusion in water-permeable tissue. As the osmolarity of ventricular CSF increases within the cerebral ventricles, water movement into the ventricles increases and causes hydrocephalus. Macromolecular clearance from the ventricles is a mechanism to establish the normal CSF osmolarity, and therefore ventricular volume. Efflux transporters, (p-glycoprotein), are located along the blood brain barrier and play an important role in the clearance of macromolecules (endobiotics and xenobiotics) from the brain to the blood. There is clinical and experimental data to show that macromolecules are cleared out of the brain in normal and hydrocephalic brains. This article summarizes the existing evidence to support the role of efflux transporters in the pathogenesis of hydrocephalus. The location of p-gp along the pathways of macromolecular clearance and the broad substrate specificity of this abundant transporter to a variety of different macromolecules are reviewed. Involvement of p-gp in the transport of amyloid beta in Alzheimer disease and its relation to normal pressure hydrocephalus is reviewed. Finally, individual variability of p-gp expression might explain the variability in the development of hydrocephalus following intraventricular hemorrhage.
IntroductionNormal pressure hydrocephalus (NPH) has conventionally been treated by placement of a ventriculoperitoneal shunt. However, it can also be treated with a less invasive technique, an endoscopic third ventriculostomy (ETV). Unfortunately, there is a lack of evidence on the characteristics of NPH patients who are most likely to benefit from ETV. This study seeks to identify if patients at risk of dementia with NPH should be candidates for an ETV. MethodologyThirty-six NPH patients who underwent ETV at two institutions between July 2007 and December 2014 were pre-surgically assessed for various risk factors. At the time of ETV, a cortical biopsy was obtained and assessed for plaques consistent with dementia. Post-procedure, patients were followed and assessed for symptoms such as gait improvement, headache, memory problems, incontinence, and dementia. ETV success was defined as an improvement in gait. ResultsThe mean age of patients with successful ETVs was 65.8 ± 6.0 versus 74.5 ± 7.0 for failed ETVs. Sixty-seven percent of patients with negative biopsies showed gait improvement by the final follow-up appointment as compared to only 33% of patients with positive biopsies (p>0.05). Younger age was correlated with successful ETV (p=.003). Memory disturbance (p<0.05) and incontinence (p<0.05) after surgery were both associated with a lack of gait improvement at the final follow-up. ConclusionBiopsy was not a significant predictor of ETV success; however, there was a correlation between younger age and ETV success. Additional studies are required to determine if there is a relationship between cortical biopsy findings and ETV success.
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