CSF Protein Markers as Prognostic Indicators of the Response to CSF Shunt in Normotensive Hydrocephalus

Overview

In all published series of adult chronic hydrocephalus, there is a percentage between twenty and twenty-five percent of patients who present poor results after implantation of a cerebrospinal fluid shunt,1-11 usually ventriculoperitoneal. The lumboperitoneal shunt is also used but much more rarely. The diagnosis of this pathology is based on the clinical picture, neuroimaging studies (Evans index and corpus callosum angle), cerebrospinal fluid dynamics tests (Katzman test), and invasive intracranial pressure measurements. Despite all this diagnostic arsenal, there is a high percentage of patients (mentioned above) in which treatment by diversion of cerebrospinal fluid does not offer the expected results. Traditionally, this has been attributed to chronic adult hydrocephalus being associated with other types of dementia. This may be the case in some patients, and it would be important to predict which patients will not improve or who will improve poorly in the case of insertion of a cerebrospinal fluid shunt.

Adult chronic hydrocephalus, also known as normal pressure hydrocephalus or normal pressure hydrocephalus, presents with the classic Hakim-Adams triad, gait ataxia or "magnetic gait", urinary incontinence, and dementia. Most cases have an idiopathic origin and constitute the only potentially reversible cause of dementia with surgical treatment (using a system for shunting the cerebrospinal fluid or CSF from the lateral ventricles or the thecal sac to the peritoneal cavity or right atrium ), so it is especially important to diagnose and treat it properly. The prevalence of this pathology is increasing in line with the increase in the life expectancy of the population. The diagnosis of this pathology is based on the clinical features, neuroimaging studies (CT and Magnetic Resonance), cerebrospinal fluid dynamics tests (Katzman test), cerebrospinal fluid drainage by lumbar puncture or using lumbar drainage for hours, and invasive measurements of Intracranial Pressure (ICP). Continuous monitoring of Intracranial Pressure with the patient admitted for 3-5 days (continuously night and day) is the most sensitive and specific diagnostic method for this disease, but it also has its false positives and negatives. Likewise, even though complications are very infrequent, it is an invasive technique that requires prolonged and continuous recordings to assess hydrodynamic changes. Unfortunately, and despite all the diagnostic arsenal, the results of treatment using cerebrospinal fluid shunts (lumboperitoneal or ventriculoperitoneal), even in the best series, yield 20-25% poor results. These poor results have been attributed to many factors, including associated cerebral vascular disease problems, coexisting dementia not always well diagnosed, and Parkinson's disease. On the other hand, the incorrect indication of a shunt can lead to unnecessary complications, potential morbidity and mortality (subdural hematomas, infections, etc.), and the low success rates mentioned above. Therefore, it is necessary to optimize the diagnosis and treatment of these patients as much as possible. In an attempt to improve the diagnostic arsenal and, above all, try to predict which patients will improve and in which areas (cognitive, motor, or sphincter control), some researchers have studied the levels of certain proteins or peptides. in the cerebrospinal fluid obtained by a lumbar or ventricular puncture to try to find some kind of correlation between the levels of these protein markers and the type of dementia (Alzheimer's, for example, or adult chronic hydrocephalus) and the response to be expected with the implantation of a cerebrospinal fluid shunt. The markers have been highly varied (amyloid β1-42, amyloid β1-40, T-tau, phospho-tau, neurofilament light chain protein, neurogranin, monocyte chemoattractant protein), and not all of them are available to all hospitals. In our environment, we have the determination in cerebrospinal fluid of the Aβ1-42 amyloid, phospho-tau, and h-tau proteins, which are the most widely used internationally. The purpose of this study is to try to see if there is a correlation between the levels of cerebrospinal fluid obtained by lumbar puncture during the practice of the Katzman test and the results of the implantation of a cerebrospinal fluid shunt and to try to find out which marker is related to which the improvement of each of the three symptoms that afflict patients with adult chronic hydrocephalus, that is, cognitive impairment, gait problems, and inadequate sphincter control.