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DOI: 10.1055/s-0046-1816554
Biochemical Parameters of Cerebrospinal Fluid of Hydrocephalus Patients: Clinical Implications in Predicting Shunt Dysfunction
Authors
Abstract
Objective
The aim of this study is to identify and establish biochemical parameters that can predict shunt blockage or malfunction in patients undergoing ventriculoperitoneal (VP) shunt surgery for hydrocephalus by analyzing cerebrospinal fluid (CSF) obtained during surgery.
Material and Methods
This retrospective study was conducted among patients with hydrocephalus who underwent VP shunt surgery in the Departments of Neurosurgery at two medical institutions during the periods 2011 to 2014 and 2021 to 2024, respectively. CSF samples were collected during shunt surgery and analyzed. Individual biochemical parameters were studied to identify potential predictive factors for shunt blockage. Each patient was followed-up for a minimum of 6 months to assess shunt malfunction or blockage. Patients with shunt malfunction due to infection or malposition were excluded.
Results
A high CSF protein value (>100 mg/dL) was found to be statistically significant in predicting the possibility of shunt blockage during follow-up in patients undergoing VP shunt surgery. The CSF protein level was also inversely proportional to the symptom-free interval following VP shunt placement.
Conclusion
The ability to predict shunt malfunction using CSF parameters prior to surgery may help a group of patients avoid unnecessary VP shunt-related complications and help surgeons in appropriate surgical planning and in explaining prognosis.
Introduction
Hydrocephalus is a term derived from Greek, meaning “water on the head.” This disease has affected mankind as early as 1500 to 500 BC, with evidence from the Olmec civilization of the Mesoamerican period, and it was also well-described in ancient Egyptian medicine. Hippocrates (400–377 BC) described the symptoms of hydrocephalus in detail. Hydrocephalus is defined as the symptomatic accumulation of cerebrospinal fluid (CSF) within the cerebral ventricles.[1]
Dandy first described and classified hydrocephalus into communicating and non-communicating types in 1913. Later on, hydrocephalus has been classified into several categories. In adults, it is classified as obstructive, communicating, hypersecretory, and normal pressure hydrocephalus. Based on etiology, hydrocephalus is classified as primary (congenital) or secondary, due to causes such as infection and tumors obstructing the common pathways of CSF flow. An association with congenital abnormalities such as spinal dysraphism, Dandy − Walker malformation, and others has been seen.[2] Hydrocephalus can also present as an acute emergency, resulting in raised intracranial pressure, temporal lobe herniation and autonomic dysfunction, coma, and deaths. Neonates or infants with hydrocephalus may have congenital causes or may develop condition associated with intraventricular hemorrhage. Excessive CSF production can occur due to tumors such as choroid plexus papilloma or carcinoma, whereas decreased absorption may result from infectious causes such as meningitis at the level of the arachnoid granulation. Other causes such as intraventricular hemorrhage or subarachnoid hemorrhage can also cause secondary obstruction to absorption of CSF at the level of the arachnoid granulations.[3]
Aims and Objective
This aim of this study is to identify and establish biochemical parameters in CSF that can predict shunt blockage or malfunction in hydrocephalus patients undergoing ventriculoperitoneal (VP) shunt surgery.
Material and Methods
This retrospective study was conducted in patients with hydrocephalus undergoing VP shunt surgery in the Department of Neurosurgery of two medical institutions during the periods 2011 to 2014 and 2021 to 2024, respectively. CSF samples were collected during shunt surgery and analyzed. Individual biochemical parameters were studied to identify potential predictive factors for shunt blockage.
Each patients were followed up for a minimum of 6 months to assess shunt malfunction or shunt blockage. Patients with shunt malfunction due to infection or shunt migration were excluded.
Exclusion criteria included shunt malfunction due to infection or malposition, patients with intracranial hemorrhage, moribund patients, and those lost to follow-up before completing the 6-month follow-up period.
The CSF parameters studied in each patient included CSF protein (mg/dL), measured using the pyrogallol red method, CSF glucose (mg/dL) measured using GOD POD method; and CSF cell count. Patients with raised CSF protein levels were divided into two groups: Group A, <100 mg/dL, and group B,≥100 mg/dL as decided according to a reference study.[4]
Statistical analysis was performed using SPSS software (version 16.0; SPSS, Inc.). Analysis included the independent sample t-test, the Chi-square test, and multivariate logistic regression.
The mean values of each parameter were calculated for the shunt malfunction group and the normally functioning shunt group and corresponding p-values were calculated.
Results
A total of 242 VP shunts procedures were performed at Institute 1 between 2011 and 2014, and 203 procedures were performed at Institute 2 between 2021 and 2024. During the study period, 17% of cases from Institute 1 presented with shunt dysfunction during follow-up ([Table 1]). Seven cases with shunt malposition or infection were excluded from our study. Out of the 203 cases from Institute 2, 13% developed shunt dysfunction in the form of shunt blockage. Five patients were excluded because of shunt migration or infection ([Figs. 1] and [2]).




Analysis of CSF Parameters with Respect to Shunt Malfunction
The p-value shunt malfunction associated with CSF protein levels greater than 100 mg/dL was <0.05, indicating statistical significance in our study ([Figs. 1] and [2]). Receiver operating characteristic (ROC) analysis showed area under the curve (AUC) of 0.75, indicating moderate predictive accuracy. Sensitivity was 70% (at 100 mg/dL cutoff) and specificity was 65% at a cut-off value of 100 mg/dL. The chi-square test also showed statistical significance (p <0.05).
[Figs. 3] and [4] illustrate cases of three and two shunt blockages, respectively.




[Tables 1] and [2] show comparative data between patients with shunt malfunction and those without malfunction.
|
| CSF protein | |
Shunt malfunction |
No malfunction |
|---|---|---|
|
| <100 mg/dL | |
10 patients |
150 patients |
|
| >100 mg/dL | |
40 patients |
50 patients |
Discussion
The complications of shunt are divided into mechanical and infective. Mechanical complications include shunt blockage, migrations, disconnection, bowel perforation, and related issues. Infective complications include ventriculitis, shunt infection, skin-site infection, scalp collection, and subdural bleeding. For a shunt to function normally, the biochemical parameters of CSF must be within normal limits, as shown in our study.[5]
There was no effective treatment for hydrocephalus until 1949, when Frank Nulsen and Eugene Spitz started the first shunt diversion technique. Later, the VP shunt became the mainstay of hydrocephalus management and remains one of the most commonly performed neurosurgical procedures. However, it is associated with a high rate of complications.[6] The overall global prevalence of hydrocephalus is approximately 85 per 100,000 individuals with significant differences across age groups: 88 per 100,000 in the pediatric population and 11 per 100,000 in adults.[3]
Diagnosis of hydrocephalus is made using clinical signs, radiological imaging, and CSF studies. Patients present with different symptoms depending on their age. In infants signs may include increase head size, thinning of the scalp, suture diastasis, dilated veins, frontal bossing, and sunset eye sign (due to pressure on the tectal plate), as well as irritability, excessive crying, seizures, and hypertonia. In adults the patient may present with features of raised ICP, diplopia, vomiting, and headache. In older adults, patients may present with normal pressure hydrocephalus, characterized by mildly elevated ICP and Hakim's triad: dementia, wide-based gait, and urinary incontinence.[7]
Evaluation with imaging is done using a CT scan of brain, which can suggest ventricular dilatation. MRI of the brain can identify underlying pathological abnormalities. CSF study, including cytology, biochemistry, and culture are performed prior to surgery. CSF can be obtained via lumbar puncture or direct ventricular tapping under sterile precautions. CSF opening pressure is also measured to help determine the need for surgical intervention. Patients with hydrocephalus need surgical management, and various surgical modalities are available.[8]
The primary treatment for hydrocephalus is the VP shunt. Other types of shunts include ventriculoatrial and ventriculopleural shunt. However, CSF must have normal biochemical parameters for the shunt to function normally. In our study, we analyzed biochemical factors that may contribute to malfunction. Shunt malfunction rates in various series range from 16 to 42.3%, which corresponds to our findings.[9]
A high CSF protein value was found to be statistically significant in predicting the possibility of shunt blockage during follow-up in patients undergoing VP shunt. The CSF protein level was also inversely correlated with the symptom-free interval following VP shunt.[10]
Ambekar et al reported that patients with shunt malfunction had significantly higher CSF protein concentrations.[4] CSF cellularity and glucose concentration did not have a significant role in predicting shunt malfunction. Patients with CSF protein concentration above 200 mg/dL had a fourfold higher risk of shunt malfunction compared with those with concentration below 100 mg/dL, while patients with CSF protein in the 100 to 200 mg/dL range represented an intermediate risk zone.[4]
In cases of high CSF protein, where there is a risk of shunt blockage, alternate procedures are considered, such as external ventricular drainage, Ommaya reservoir placement, ventriculo-subgaleal shunt, serial lumbar punctures, and ventricular punctures.
Despite all precautions, shunt are associated with “n” number of complications. In the study by Agarwal et al, 34.14% of patients with shunt-related complications presented within 6 months of shunt placement and 51.21% presented within 2 years. Literature review shows event-free survival at 1 year ranges from 62 to 80%[4] [11] and at 10 years from 35 to 48%.[11]
Conclusion
Shunt malfunction associated with CSF protein levels more than 100 mg/dL was found to be statistically significant in our study, consistent with findings in our literature. The predictability of CSF parameters for shunt malfunction prior to surgery can help patients avoid unnecessary complications of VP shunts and help surgeons in appropriate surgical planning.
Limitations
This study has several limitations. Other causes of raised CSF proteins were not fully explored. ROC analysis was performed for the 100 mg/dL cutoff, but larger studies are needed to validate these findings.
Conflict of Interest
None declared.
Acknowledgment
The authors acknowledge SOA University for the unconditional support.
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References
- 1 Aschoff A, Kremer P, Hashemi B, Kunze S. The scientific history of hydrocephalus and its treatment. Neurosurg Rev 1999; 22 (2-3): 67-93 , discussion 94–95
- 2 Rekate HL. Classifications of hydrocephalus based on Walter Dandy and his paradigm. Childs Nerv Syst 2023; 39 (10) 2701-2708
- 3 Koleva M, De Jesus O. Hydrocephalus. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2025
- 4 Ambekar S, Dwarakanath S, Chandramouli BA, Sampath S, Devi BI, Pandey P. Does CSF composition predict shunt malfunction in tuberculous meningitis?. Indian J Tuberc 2011; 58 (02) 77-81
- 5 Deo RC, Acharya A, Senapati SB, Panigrahi S, Mohapatra AK. Complete intraventricular migration of ventriculo-peritoneal shunt: a rare case report. Int J Surg Case Rep 2022; 101: 107772
- 6 Boockvar JA, Loudon W, Sutton LN. Development of the Spitz-Holter valve in Philadelphia. J Neurosurg 2001; 95 (01) 145-147
- 7 Fink KR, Benjert JL. Imaging of nontraumatic neuroradiology emergencies. Radiol Clin North Am 2015; 53 (04) 871-890 , x
- 8 Korbecki A, Zimny A, Podgórski P, Sąsiadek M, Bladowska J. Imaging of cerebrospinal fluid flow: fundamentals, techniques, and clinical applications of phase-contrast magnetic resonance imaging. Pol J Radiol 2019; 84: e240-e250
- 9 Fowler JB, De Jesus O, Mesfin FB. Ventriculoperitoneal Shunt. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2025
- 10 Rei KM, Ghauri MS, Uddin MB, Siddiqi J. Ventriculoperitoneal shunt failure and cerebrospinal fluid protein: a meta-analysis and systematic review. Cureus 2024; 16 (02) e54362
- 11 Agarwal N, Shukla RM, Agarwal D. et al. Pediatric ventriculoperitoneal shunts and their complications: an analysis. J Indian Assoc Pediatr Surg 2017; 22 (03) 155-157
Address for correspondence
Publication History
Article published online:
04 February 2026
© 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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References
- 1 Aschoff A, Kremer P, Hashemi B, Kunze S. The scientific history of hydrocephalus and its treatment. Neurosurg Rev 1999; 22 (2-3): 67-93 , discussion 94–95
- 2 Rekate HL. Classifications of hydrocephalus based on Walter Dandy and his paradigm. Childs Nerv Syst 2023; 39 (10) 2701-2708
- 3 Koleva M, De Jesus O. Hydrocephalus. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2025
- 4 Ambekar S, Dwarakanath S, Chandramouli BA, Sampath S, Devi BI, Pandey P. Does CSF composition predict shunt malfunction in tuberculous meningitis?. Indian J Tuberc 2011; 58 (02) 77-81
- 5 Deo RC, Acharya A, Senapati SB, Panigrahi S, Mohapatra AK. Complete intraventricular migration of ventriculo-peritoneal shunt: a rare case report. Int J Surg Case Rep 2022; 101: 107772
- 6 Boockvar JA, Loudon W, Sutton LN. Development of the Spitz-Holter valve in Philadelphia. J Neurosurg 2001; 95 (01) 145-147
- 7 Fink KR, Benjert JL. Imaging of nontraumatic neuroradiology emergencies. Radiol Clin North Am 2015; 53 (04) 871-890 , x
- 8 Korbecki A, Zimny A, Podgórski P, Sąsiadek M, Bladowska J. Imaging of cerebrospinal fluid flow: fundamentals, techniques, and clinical applications of phase-contrast magnetic resonance imaging. Pol J Radiol 2019; 84: e240-e250
- 9 Fowler JB, De Jesus O, Mesfin FB. Ventriculoperitoneal Shunt. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2025
- 10 Rei KM, Ghauri MS, Uddin MB, Siddiqi J. Ventriculoperitoneal shunt failure and cerebrospinal fluid protein: a meta-analysis and systematic review. Cureus 2024; 16 (02) e54362
- 11 Agarwal N, Shukla RM, Agarwal D. et al. Pediatric ventriculoperitoneal shunts and their complications: an analysis. J Indian Assoc Pediatr Surg 2017; 22 (03) 155-157









