Clinical trial NCT05915000: CSF Protein Markers As Prognostic Indicators of the Response to CSF Shunt in Normotensive Hydrocephalus
Official title: Alterations of CSF Protein Markers As Prognostic Indicator of the Response to Cerebrospinal Fluid Shunting in Chronic Hydrocephalus in Adults
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Beta-amiloid and Phospho-tau Proteins in CSF
Ventricular Size After CSF Shunt
Cognitive Impairment and CSF Shunt
Motor Impairment Evolution After CSF Shunt
Keywords: Hydrocephalus
Normal pressure hydrocephalus
CSF shunt
Cognitive impairment
Lead sponsor: University of Valencia
Sponsor class: OTHER
First posted: 2023-06-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study sample will be made up only of patients who meet the suspected diagnosis of adult chronic hydrocephalus, who are the ones who are going to have the valve implanted and followed up over time. In addition, the sample will be extracted with the biomarkers. The presence or absence of these biomarkers and their levels will be correlated with the clinical evolution of the patients so that these biomarkers could be used as prognostic indicators or to early identify those subjects in whom the cause of the symptoms was not really hydrocephalus but incipient dementia of another type (or other pathology).

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Minimum age of 18 years, there is no maximum age, especially if it is understood that this pathology is more frequent as one advance in age, especially among males; pathology compatible with chronic adult hydrocephalus

Exclusion Criteria:

* All patients whose suspected diagnosis is not adult chronic hydrocephalus will be excluded, specifically those with cerebrovascular disease, dementia not due to adult chronic hydrocephalus, Alzheimer's disease, Parkinson's disease, and hereditary degenerative brain pathology. Huntington's chorea

Primary outcomes:
measure: Correlation between lumbar CSF protein markers and response to CSF shunt in normal pressure hydrocephalus
timeFrame: 1 year
measure: Lumbar CSF protein marker levels that recommend no CSF shunt in normal pressure hydrocephalus
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Vicente Vanaclocha
Study officials:
References:
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