Literature Review of Ventriculoperitoneal Shunt Dysfunction Rates and Risk factors

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LITHUANIAN UNIVERSITY OF HEALTH SCIENCES MEDICAL ACADEMY

DEPARTMENT OF NEUROSURGERY

Literature Review of Ventriculoperitoneal Shunt Dysfunction Rates and

Risk factors

Ilan Tzaytlin Faculty of medicine VI

Group 34

Supervisor: Prof. Vytenis Pranas Deltuva, M.D. PhD

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1. Summary

Aim: To review ventriculoperitoneal shunt dysfunction rates and risk factors

Objectives: Ventriculoperitoneal (VP) shunting is a commonly used neurosurgical procedure to treat

hydrocephalus, but it has a high failure rate. VP shunt malfunction is frequently caused by shunt infection and proximal or distal shunt obstruction. This study aimed at assessing rates of shunt failure and to determine the incidence and causes of VP shunt.

Methods: The search strategy involved the key terms pertaining to the concepts; to reach maximum

sensitivity, a combination of the terms “Ventriculoperitoneal shunt”; “VP shunt malfunction”; “risk factors of shunt failure”; “shunt infection”; proximal obstruction of ventriculoperitoneal shunt“; shunt overdrainage“ and “shunt revision” were considered. Only articles that specifically discussed VP shunt malfunctions and risk factors were included.

Results: It was studied that the most common causes of VP shunt malfunction were shunt obstruction and

shunt infection.

Conclusion: VP shunt malfunction is frequent in young individuals, mostly caused by shunt obstruction

and infection. Future researches should focus on techniques designed to prevent these complications or on alternative management for hydrocephalus.

Keywords

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2. Acknowledgment

I would like to thank the Neurosurgery institute and my supervisor.

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5. ABBREVIATIONS

VP Ventriculoperitoneal CI Confidence interval CSF Cerebrospinal fluid CP Choroid plexus HR Hazard ratio OR Odds ratio VPS Ventriculoperitoneal shunt

PICO Populations/People/Patient/Problem, Intervention(s), Comparison, Outcome

PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RCTs Randomized controlled trials

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6. Terms

Hydrocephalus- is a clinical condition that is characterized by the disruption in normal CSF flow. VP shunt- a medical device that relieves pressure on the brain caused by fluid accumulation

Shunt malfunction- is a partial or complete blockage of the shunt that causes it to function intermittently

or not at all

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7. INTRODUCTION

Ventriculoperitoneal (VP) shunt placement is the most common technique for cerebrospinal fluid (CSF) diversion. For many patients with hydrocephalus, the primary surgical intervention is the placement of a shunt as an effective CSF diversion procedure shunting the CSF from the cerebral ventricles to the peritoneal cavity [1]. The placement and revision of the ventriculoperitoneal shunt remain a mainstay in the surgical management of hydrocephalus. It is relatively less complicated and is performed on patients of all ages with hydrocephalus from any cause like myelomeningocele, preceding meningitis, preceding subarachnoid hemorrhage, CNS tumor, postoperative adhesion, head trauma, other congenital

malformations and other acquired etiologies [2]. Ventricular shunts have modified the prognosis for individuals with hydrocephalus, and most acquire fairly normal intelligence.

However, shunt malfunction results in patient morbidity, mortality, and finally increases procedure costs. Despite recent developments in shunt valves and imaging studies, overall shunt survival has increased only modestly in patients with shunt-dependent hydrocephalus over the last many years. In many

healthcare facilities, the proportion of shunt placement to subsequent surgical revision is 1 to 2.5 [3]. The failure rate by one year after implantation is 25 to 40% [4].

Proximal shunt malfunction is a major cause of shunt failure in the general population. It is caused by obstruction of shunt tip by both pathological and natural tissue surrounding tissues such as choroid plexus, glial tissue, and connective tissues [5]. It is thought that shunt placement in the frontal horn of the lateral ventricle and anterior to the foramen of Monro, lowers the possibility of obstruction and subsequent shunt malfunction. Despite extensive utilization of radiological imaging techniques, including endoscopy, ultrasonography, and contrast guidance, as well as intraoperative neuronavigation, the failure rate for shunts within several years exceeds 30% [6]. Shunt malfunction can also result from shunt infection, shunt fracture, shunt migration, shunt displacement, or over-drainage. Distal shunt migration, where the

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Infection is a relatively common cause of shunt malfunction, which contributes significantly to high morbidity and mortality. In many recent studies, the case incidence of shunt infection has ranged from 8% to 40%. Most infections present in the early postoperative period which demonstrates that the

perioperative contamination from the patient's skin during the surgical procedure may be a causative mechanism. [9,10]

This literature review aimed at assessing the rates of VP shunt dysfunction and common risk factors, causes of shunt failure and to assess the incidence and etiology of VP shunt failure in patients treated for hydrocephalus, to establish firm evidence-based guidelines to prevent VP shunt failure. We also

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8. AIM AND OBJECTIVES

Aim

To review ventriculoperitoneal shunt dysfunction rates and risk factors

OBJECTIVE OF THE STUDY

To evaluate the causes of ventriculoperitoneal dysfunction.

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9. RESEARCH METHODOLOGY

Review Construction:

PRISMA protocol was utilized to ensure a standardized approach to the development of this review [30]. The PRISMA protocol is an evidence-based minimum set of entities for reporting in systematic reviews and meta-analyses. This review takes the form of descriptive analysis, as the studies present

epidemiological data, of a cross-sectional design.

Records identified through database searching (n = 874) Sc re ening lude d El igi bi lity Ide ntif ic ation

Records after duplicates removed (n = 541) Records screened (n = 100) Records excluded (n = 40) Full-text articles assessed for eligibility

(n = 60)

Full-text articles excluded, with reasons

(n =7)

Studies included in systematic review

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Search Strategy:

Electronic databases PubMed, NCBI, Elsevier, UpToDate, ResearchGate, Medline, Embase, CINAHL, Cochrane, and Web of Science were evaluated. The search strategy involved the key terms pertaining to the concepts; to reach maximum sensitivity, a combination of the terms “Ventriculoperitoneal shunt”; “VP shunt malfunction”; “risk factors of shunt failure”; “shunt infection”; and “shunt revision surgery” were considered. Studies were retrieved and involved after reading the title and abstract of the study. The author further went through the reference lists of identified studies to evaluate any additional studies.

Selection criteria

This study used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to make the basis of selection criteria using the PICO (P - Populations/People/Patient/Problem, I - Intervention(s), C - Comparison, O - Outcome) worksheet and search strategy as shown in table 1.

Randomized controlled trials, case-control studies, and cohort studies fulfilling the following criteria were included: (1) English language, (2) studies from the last 10 years (3) studies conducted on Humans only, and (4) report of any considered outcomes (mortality, complications, need for further intervention). If multiple trials or studies were published by the same center, only the most complete one was included. Studies that were excluded include: (1) studies with more than 10 years of publication (unless publication has extreme relevance up to this day) (2) Nonrelevant articles by abstract and content and (3) Case reports, editorials, letters, and studies having duplicate data or already published data.

Data collection, evaluation of study quality, and risk of bias

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Table 1. PICO (Patients, Intervention, Comparison, Outcome) worksheet

Population Patients with VP shunt failure

Intervention Ventriculoperitoneal shunt

Comparison Direct comparison with other management methods.

Outcome Shunt failure due to any cause and whether the need for further management; with no time limitation.

Statistical Analysis

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10. REVIEW OF LITERATURE

The use of VP shunts to treat hydrocephalus in both children and adults has made it one of the most common neurological intervention. Among the pediatric neurosurgical practice, it is the commonest surgical management. There are few procedures performed by neurosurgeons that are so simple, yet the same time so unforgiving, such as cerebrospinal fluid (CSF) shunt insertion.

10.1 Cerebrospinal fluid and Hydrocephalus

10.1.1 Cerebrospinal fluid circulation

Cerebrospinal fluid (CSF) has an essential role in normal brain function, and changes in its

constituents, flow, or change in intracranial pressure can negatively affect normal brain function. Equally, abnormal brain function can affect the CSF, so collection and analysis of CSF can, therefore, provide important information to assist neurological diagnosis. Dynamics in CSF amounts are dependent on the balance between its production and drainage. The CSF is located inside the ventricular system of the brain as well as in the subarachnoid spaces in the cranium and the spinal canal. It functions as a “shock

absorber” in mechanical head injuries and as a medium for transferring nutrients and waste products, to and from the brain. In adults, the volume of CSF ranges between 125 and 150 ml, of which approximately 20% is contained within the ventricles. Approximately 80% of the CSF is produced by the choroid plexus in the lateral, third, and fourth ventricles. A smaller amount of fluid is produced by the ependymal cells in the ventricles, arachnoid membrane, and brain tissue itself. The rate of production is about 25 ml/h and about 500 ml/day in adults. CSF volume in infants is about 15 ml/kg.

The pathway of CSF circulation is demonstrated in figure 1. It flows through intraventricular openings (foreman Monro) from the lateral ventricles to the third ventricle and goes onward into the fourth ventricle by the cerebral aqueduct. From there the CSF flow splits into 2 spaces

1) The CSF fills the subarachnoid space, both in its cranial and spinal parts 2) CSF fills the spinal central canal.

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Fig. 1 CSF flow inside the brain

Schematic diagram of CSF flow. 1 CSF produced by the CP (red). 2 CSF moves from lateral ventricle to the 3rd ventricle via the interventricular foramen. 3 CSF moves from 3rd ventricle to 4th ventricle via the cerebral aqueduct. 4 From the 4th ventricle CSF can either: a continue within the ventricular system and

flow through the spinal canal or, b flows into the subarachnoid space via the foramen of Magendie (located medially) or via the foramina of Luschka (located laterally). 5 The CSF that flows into the subarachnoid space (cranial and spinal) is reabsorbed into the systemic circulation via the arachnoid villi into the

dural-venous sinuses. [35]

10.1.2 Historical background

The presence of CSF was described by the author of Edwin Smith Papyrus in the eighteenth-century B.C. Existence of hydrocephalus was reported by Hippocrates. Modern knowledge of the secretion and absorption of CSF was developed by Weed in the first part of this century, while Dandy and Blackfan are known for developing the concepts of the pathophysiology of hydrocephalus that led to the successful management [11]. A review of the medical procedures that have been utilized in the management of hydrocephalus places the evolution of modern surgical practices in a favorable perspective.

Hydrocephalus was managed before the era of scientific medicine, by the usual armamentarium of uncritically selected and totally ineffective procedures: venesection, cupping, leeching purgatives, diuretics, and so on [12]. Diversion of CSF directly into the peritoneal cavity was attempted as early as 1898, and there were early attempts to utilize the pleural space and vessels as receptacles for CSF as well [13]. In 1908, the first ventriculoperitoneal shunt was placed by Kaush, who used a rubber tube to connect the lateral ventricle with the peritoneal surface. The widespread use of ventricular shunting was achieved following the introduction of unidirectional valves and biologically inert silicone elastomer tubing. A slit valve was introduced by Holter in the mid-1950s. It became one of the most widely used shunt valves globally at that time. Before VP shunting had achieved widespread use, there were reports of procedures to shunt CSF from the cerebral ventricles or subarachnoid space to any body cavity. The high

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modern VP shunts, which remains the surgical procedure of choice for the management of hydrocephalus today [14].

10.1.3 Hydrocephalus

Hydrocephalus is a clinical condition that is characterized by the disruption in normal CSF flow. This disruption may occur in production, absorption, or mechanical obstruction to the flow of CSF and is usually associated with the enlargement of ventricular size. These changes in CSF dynamics may be caused by congenital brain malformations or by many disease processes occurring within the ventricle, the brain parenchyma, or the subarachnoid spaces leading to hydrocephalus. There are several causes: in utero causes of hydrocephalus involve aqueductal stenosis, spina bifida (Chiari malformation,

myelomeningocele), and Dandy-Walker malformations [15]. Most important non-CNS associations include trisomy 13 and 18, achondroplasia, pulmonary and renal hypoplasia, transposition of the great vessels, endocardial cushion defects, hydronephrosis, esophageal atresia, omphalocele, and intestinal malrotation. Post hemorrhagic hydrocephalus is common in premature infants. Etiologies of childhood hydrocephalus include mainly congenital aqueductal stenosis and primary CNS tumors like astrocytomas, medulloblastomas, gangliogliomas, craniopharyngiomas, and ependymomas. Other etiologies include bacterial meningitis, trauma, and other congenital abnormalities. Acquired hydrocephalus in adults has many various causes. Tumor related hydrocephalus is prevalent with posterior fossa neoplasms,

suprasellar tumors, and third ventricle and pineal region neoplasms. Vascular causes include vein of Galen malformations, giant midline aneurysms, and subarachnoid hemorrhages [16].

10.1.4 Diagnosis and clinical features

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ventriculomegaly and hydrocephalus in children [36]. Magnetic resonance imaging (MRI) is considered to be more sensitive in the diagnosis of hydrocephalus, determining sites of obstruction as well as lesions not shown by CT [18].

10.2 Ventriculoperitoneal shunt

10.2.1 Procedure

Two body cavities are connected during the procedure, the ventricle, and the peritoneal cavity. (Fig2). The ventricular catheter is placed inside the ventricle, most commonly at the anterior horn of the lateral ventricle, as close to the foramen of Monro as possible. Common locations for approaching the ventricle are directly above the ventricle or from the occipital area of the ventricle (Fig. 3). In some cases, the tip of the proximal catheter is placed into the third ventricle. The ventricle is cannulated using the landmarks with the proximal catheter on a stylet. The stylet is removed as soon as the ventricle is reached, and the and distal part of the proximal catheter is connected to the valve. It is important to pay attention to connecting according to the directional arrow for the correct CSF flow direction. To reach the abdominal cavity, a subcutaneous tunnel is created from the scalp to the abdominal incision site, with the help of a blunt salmon passer. The tunnel is created by pushing a hollow metal tube down through the soft tissues under the skin, above the fascia of the neck and chest muscles. The distal catheter is introduced through the subcutaneous tunnel. The site of entry of the distal peritoneal catheter into the peritoneal cavity is at the highest point on the abdomen to achieve the shortest distance possible from ventricle to peritoneum; sub-xiphoid or subcostal usually just under the liver is the most commonly used sites to reach peritoneum during VP shunt placement. A CSF specimen is taken from the distal catheter to ensure adequate flow. Then the posterior rectus sheath is incised, the peritoneum is identified, and the distal catheter is placed intraperitoneally under direct vision. The total length of the distal catheter is about 120 cm, which could be sufficient for the entire life of the patient, even when inserted in children or newborns. The anterior rectus sheath is closed with absorbable suture, and subcuticular abdominal sutures are placed. The scalp wound is closed with absorbable sutures and applying nylon sutures on the skin. [19,20,21,38]

10.2.2 Shunt revision

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Fig 2. VP shunt structure[56] Fig.3 Illustration demonstrating trajectories for placement of a ventricular catheter [55

10.2.3 Indications and contraindications for VP shunt insertion

Hydrocephalus is the main indication for VP shunt insertion and should be managed via shunting if it is progressive, whether symptomatic or asymptomatic. Contraindications of shunt placement involve: ventriculitis, sepsis, acute intra-ventricular hemorrhage, hydrocephalus due to manageable obstructive disorders, on the basis of extreme brain pathology (i.e. hydranencephaly), asymptomatic, non-progressive hydrocephalus and ventriculomegaly without raised intracranial pressure [22].

10.2.4 Shunt complications

VP shunting is associated with a wide variety of complications which include: 1) Infections, and wound complications

2) Proximal and distal shunt obstruction leading to shunting malfunction 3) Seizures

4) Extra cerebral fluid collections 5) Subdural hematomas

6) Spontaneous pneumocephalus 7) The over-drainage syndrome 8) Ascites

9) Bowel perforation

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10.3 Shunt failure and risk factors

Shunt dysfunction is a relatively frequent complication of shunt placement, with most authorities quoting a rate of approximately 7 to 10 percent per procedure, which contributes significantly to excess morbidity and mortality [23]. VP shunt malfunction present with the signs and symptoms of

hydrocephalus that are typical for the patient’s age group. Infants with a shunt malfunction usually present with irritability, lethargy, vomiting, the fullness of the fontanelle, and rapidly increasing head

circumference. Older children present with headaches, nausea, vomiting, and irritability. The signs of VP shunt malfunction are usually progressive, but they may wax and wane sometimes. It is important to ask the patient and the family about the symptoms that were present with prior shunt failures [19].

Radiological studies should be considered in children with suspected shunt failure after a careful history and general physical examination. A head CT is important to assess variations in ventricular size, and plain radiographs of the head and abdomen are also helpful to evaluate any disconnections or kinks in the shunt tubing. Although the majority of patients with VP shunt malfunction present with widened

ventricles, there exists a subset of patients in whom ventricular size does not change due to decreased compliance (frozen ventricles) [26].

The risk factors for shunt malfunction were discussed in academic literature, however, there appears to be no clear agreement among various authors and clear risk factors for VP shunt infection are still not well known. Table 1 presents the results from different studies.

Reddy et al. [39] mention that male gender (OR=1.67), etiology of hydrocephalus (OR=1.94), most common being congenital, and placement of the shunt in the age younger than 17 (OR=3.18) all lead to increase in infection rates in VP shunt patients with clinical significance.

Erps et al. [40] show that children that had two or more shunt revisions (OR=4.8), aged less than 5 years old (OR= 4.5) showed a statistical correlation with shunt infections. Lee et al. [41] specify their age of risk to less than 1 year old (RR=2.31). Also, they show that there is a significance to the etiology of the

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Table 2. Risk factor for shunt malfunction

First Author Year of Publication

Study Population (n)

Study Design Risk factors with clinical significance for shunt malfunction

Reddy et al. 2012 1015 Retrospective cohort *Male gender

*Congenital cause for shunt insertion

* Age younger than 17 years old at the time of shunt insertion

Erps et al 2018 1570 Single-center,

retrospective review

*First surgery at younger than 5-years-old

*2 or more shunt revisions

Lee et al. 2012 333 Retrospective cohort *First surgery at younger than 1 year old

* Etiology of intracranial hemorrhage

Simon et al. 2014 1036 multi-center

prospective cohort study

*Presence of gastrostomy tube at the time of shunt placement.

Ahmadvand et al. 2019 403 Retrospective cohort *Surgeons experience

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Although the information that is derived from the reviews is not decisive, it shows a general picture of risk factors that are needed to be taken into consideration in VP shunt patients, and if they are preventable, to try and adjust them before the surgery for the protection of the patients.

10.4 Causes of shunt malfunction

10.4.1 Shunt obstruction

Mechanical obstruction of the shunt is the most common cause of shunt failure, occurring at a frequency of up to 50% by 2 years post-implantation. VP shunts should be considered as mechanical devices that can malfunction or become occluded anywhere along their course at any point in their lifetime.

The VP shunt proximal catheter is the most common site of malfunction, and it was considered that occlusion of the ventricular catheter was due to choroid plexus or debris inside the ventricle. It is now evident that majority of these failures are due to the migration of astrocytes and microglia into the perforations of the catheter.

The valve mechanism of the shunt may also become obstructed because of mechanical failure or clogging with debris as they migrate with the anterograde flow of CSF. It can also happen by direct embolization of clotted blood products generated at the time of ventricular catheter placement.

Distal catheter obstruction is the rarest malfunction of the three components, coming at roughly 5-15% of the cases. It tends to occur in a delayed fashion, as a result of breakage in the tubing or withdrawal from the peritoneal cavity. Infection and inflammation may also cause a palpable pseudo-cyst to form around the tip of the catheter in the peritoneal cavity, leading to blockage of CSF drainage, a rare complication that occurs in 1-4.5% of patients.

An obstructed shunt usually is a medical emergency, requiring prompt reoperation. Each part of the shunt is evaluated independently, and any malfunctioning component is replaced [24,25,26,32,43,44,45,46,49].

10.4.2 Shunt Over and Underdrainage

Some individuals are very prone to increase or decrease in intracranial pressure and develop

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caused by reduced drainage are typically worse when recumbent, whereas headaches due to increased drainage are worsened by erect position, as well as in under-drainage situations, headaches occur in 100% of patients [44]. In some cases, individuals experiencing excessive drainage will have smaller ventricles on imaging. Patients should undergo a careful investigation to ensure that the shunt has not failed [27]. A possible dangerous complication of over-drainage is non-traumatic subdural hematoma, which may aggravate the symptoms of the over drainage. It can be treated by adjusting the rate of drainage but may require evacuation with surgery [51,53].

10.4.3 Shunt Infection

The ventricular catheter, valve, and peritoneal tubing are all foreign bodies that can harbor bacteria introduced by contamination at the time of surgery or by seeding of organisms introduced into the

bloodstream by a variety of surgical and non-surgical procedures. The incidence of VP shunt infection and infection rate varies from study to study. Incidence rates averages between 3-20% and can go up to 39% of the recent studies and the incidence ranges from 5-10% [48]. The incidence of shunt infection is a serious complication that is related to high morbidity and mortality. Most of the infections occur shortly after surgery: with more than 70% occurring within one month and 90% occurring within six months [28]. However, the proportion of shunt failures related to infection decreases substantially after the first six months, as the infection rate 2 years after implantation was only 6% of failures [49]. Patients generally present with fever, headache, generalized malaise, leukocytosis, and elevated inflammatory markers. Erythema of the surgical site or shunt tract may also be noticed. Infectious debris may obstruct the shunt, causing a superimposed shunt malfunction. In some circumstances, bacteria move through the shunt tubing, causing peritonitis, bacteremia, or endocarditis, depending on the site of the distal catheter. Patients with symptoms of peritonitis and shunt failure should undergo imaging techniques(ultrasound or abdominal CT) to rule out a pseudo-cyst. Brain imaging may show enlarged ventricles if the shunt has malfunctioned.

The majority of shunt infections are due to contamination at the time of the surgical procedure, and thus skin’s flora is the most common microbes involved. Staphylococcus epidermidis is the most common cause of shunt infection. Staphylococcus aureus is responsible for approximately one-third of the cases. The remaining cases are due to other gram-positive cocci, gram-negative organisms, and anaerobes. Risk factors for shunt infection include young age, the presence of a gastrostomy tube, a history of

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Both antibiotic-impregnated and silver-coated catheters were designed with the goal of reducing shunt infection complications and have become widely adopted. Although both showed a reduction in

postoperative infection rates, it was noted that that the infection that did occur, were due to more virulent organisms [5,29].

10.4.4 Shunt Fracture

It occurs as a late complication and most commonly in the distal part between the valve and the distal tip in the peritoneum. Although the catheter spouse to be flexible and slide freely between the subcutaneous tract. With time, the material hardens and calcifies which increases the risk for fractures. The incidence of fractures is approximately 3-21% of all shunt failures. As the tube breaks, the CSF flow decreases or stops completely which may cause fulminant or more insidious hydrocephalus. Plain X-Ray is used to identify the broken fragments of the VP shunt tube and should be done in suspicion of a fracture [49].

10.4.5 Shunt Disconnection

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RESULTS

The search strategy resulted in an initial yield of 874 abstracts, of which 333 were duplicates. Titles and abstracts were reviewed, and 100 articles were found to be of relevance. The full texts of 100 articles were retrieved and examined. 40 were excluded using the exclusion criteria. 60 studies were retrieved that provided answers to the target questions. 12 were included in the final review (Table 3&4) as other studies showed the absence of clear data required in our inclusion criteria. These thirteen studies were arranged in a table constructed to aid data review and analysis.

Table 3. Summary of publications used in the review

First Author Year of Publication

Study

Population (n)

Study Design Population

Merkler et al. 2018 17035 Retrospective cohort Adults

Korinek et al 2011 720 Prospective, randomized comparative trial Adults

Spirig et al. 2017 148 Single-center, retrospective review Adults

Reddy 2012 133 Single-center, retrospective review Adults

Turhan et al 2012 38 Single-center, retrospective review Pediatrics

Khan et al. 2013 113 Prospective, randomized comparative trial Pediatrics

Bakhsh 2011 100 Single-center, retrospective review Pediatrics

Shannon et al 2014 237 Single-center, retrospective review Pediatrics

Beez et al. 2012 73 Single-center, retrospective review Pediatrics

Miranda et al. 2011 103 Retrospective review Pediatrics

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Tuli et al. 2013 839 Prospective cohort study, Pediatrics

Shannon et al. [31] included 237 individuals in the study at the time of shunt placement. It was reported that about half of these patients experienced shunt malfunctions within a follow-up period of two years. The majority of shunt malfunctions were caused by infection or a proximal occlusion. Beez et al [11] evaluated shunt malfunction in seventy-three patients. He reported shunt failure in twenty-three of them (64%). Miranda et al. [19] reported VP shunt malfunction in 103 patients with post-hemorrhagic

hydrocephalus and studied that forty-two VP shunts (40.8%) lead to an initial proximal obstruction within few months of follow-up, eight of these developed due to a previous shunt infection and few cases (10%) developed occlusion without previous infection. Turhan et al. [12] evaluated thirty-eight in whom multiple shunt malfunctions were developed. Shunt infection was the most common etiology of shunt malfunction followed by distal obstructions, proximal obstruction, valve malfunctions, and four pseudo-cysts.

Complete displacement of the VP shunt was reported in two patients. Malposition of the ventricular catheter was also reported in some patients. Bakhsh et al. [17] studied a 100 cases of infantile

hydrocephalus among which a total of 14 patients (14%) presented with shunt infection (including 4 with acute shunt infection), 10 patients (10%) developed shunt obstruction (4 within the first few months and 6 within the second year after the procedure).

Tuli et al. [33] found no valve type to be linked with shunt malfunction in a post hoc analysis of a prospective cohort of patients who underwent primary shunt placements. In addition, no association between shunt malfunction and any component of the shunt hardware was identified in that report. However, they did conclude that the timing from the shunt procedure is significant: a surgical revision performed in less than 6 months from the preceding implantation results in an increased risk of additional failure. Retrospectively, McGirt et al. [34] reviewed 279 patients who have had shunt placement

procedures. The authors found that the use of programmable valves was associated with a reduced risk of both complete shunt revision and proximal shunt obstructions.

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was established in studies that were done in the last 40 years. Korinek et al. [52] the main cause of shunt failure was shunt obstruction. To lower the dysfunction rate due to this reason, they suggest avoiding to perform the procedure in cases when CSF protein or cell counts are elevated and thoroughly flush the catheter during surgery. The shunt infection rate in this study was on the lower end of previously reported ranges. Spirig et al. [44] showed the second-highest percent (46%) of shunt dysfunction in adult studies in this review. They investigated the complications and stratified them into a timeline of their highest

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Table 4. Outcomes in main published studies ventriculoperitoneal shunt dysfunction.

First Author Study population Infection% Over-drainage% Obstruction% Fracture/ Disconnection% Total dysfunction rate

Merkler et al. 17035 6% n/a n/a n/a 24%

Korinek et al 720 6% 5% 16% 0.8% 37%

Spirig et al. 148 5% 3% 9% n/a 46%

Reddy 255 4% 8% 5% n/a 52%

Adult Range 4-6% 3-8% 5-16% n/a 24-52%

Turhan et al 153 24% 0.6% 78% 4% n/a

Khan et al. 113 8% n/a 15% n/a 23%

Bakhsh 100 14% n/a 10% n/a 10%

Shannon et al 439 25% n/a 25% n/a 45%

Beez et al. 100 6% n/a _14% n/a _50%

Miranda et al. 103 13% n/a 41% n/a n/a

McGirt et al. 281 6% n/a 29% 6% 48%

Tuli et al. 839 19% 6% 67% n/a 54%

Pediatric average

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DISCUSSION

This review was started with global research of literature for studies focused on VP shunt

malfunction. During the process of this review, every single abstract was evaluated for the possibility of data for this systematic review meeting inclusion criteria.

Ventriculoperitoneal (VP) shunt insertion is a relatively common neurosurgical procedure performed for the management of hydrocephalus and associated disorders in which the flow of cerebrospinal fluid (CSF) is impeded. Though VP shunt is one of the commonest neurosurgical procedures done globally,

complications are equally high and cumbersome to treat. Shunts are quite susceptible to defect, which contribute to high morbidity and mortality. The shunt failure due to various causes requires shunt revision which has been reported as high as 10 to 20% in various studies within the first few months of shunt placement [1,9,11].

The most frequent causes of shunt malfunction are shunt obstruction and shunt infection. Risk factors for shunt infections involve a young age group, previous history of infections, causes leading to

intraventricular hemorrhage, glove holes during the procedure, contamination through skin wound, and CSF leakage post-surgery. The vast majority of VP shunt infections occur due to contamination by microbial organisms during shunt insertion however infections might also develop due to hematogenous spread, peritonitis, and abdominal pseudocyst formation [23].

VP shunt obstruction is another most common cause of shunt malfunction. The most frequent site of shunt obstruction reported in studies is the proximal catheter. Growth of choroid plexus within the shunt pores, collapsed ventricle after drainage of CSF which might press the catheter tip, blood clots, and tissue debris are the main causes responsible for obstruction of this site [3,26]. Obstruction of the distal catheter is not as frequent as the proximal catheter and the most common etiologies of obstruction are peritoneal debris, kinking of the tube, and abdominal pseudocyst formation [18,19].

Several cohort studies have reported the young age group and male sex to be major risk factors for VP shunt malfunction [27,40,41].

In their review, Beez T et al. statistically significant difference was found between shunt revision

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In comparing the approach for proximal catheter placement, it was not found that any approach had major statistical significance when comparing occipital and frontal approaches. On the other hand, it was found that a bigger influencing factor was the proximity of the proximal catheter to the choroid plexus. The higher rates of obstruction occur in frontal approaches done only in cases where EVD’s are placed before VP shunt insertion [21,59,60].

As for the placement of the proximal catheter tip, rates of dysfunction were observed to be 2-6 times higher, when the tip was placed in Septum pellucidum or when contacting the Wall of the lateral ventricle in comparison to placement into third ventricle or body of lateral ventricle [38, 57].

Intraventricular hemorrhage, a younger age, male gender and lower weight at the time of VP shunt

insertion in children, were shown to be directly associated with an increased risk of VP shunt malfunction [15,39]. Few articles also add that the presence of gastrotomy tube, as well as surgeons' experience, increases the risk for complications [42,47]. Miranda et al. [25] reported that rates of shunt obstruction in post-hemorrhagic hydrocephalus were high but did not seem to be higher than in other groups with hydrocephalus. On the other hand, normal pressure hydrocephalus (NPH) was found to have the lowest rate of shunt malfunctions. A possible explanation for this is the large size of ventricles in patients with NPH, which decreases the possibility of the proximal catheter to become obstructed [58].

This review reports that most VP shunt failures are caused either by obstruction or infection, rather than by other causes of shunt failure such as valve problems, displacement, kinking, or disconnection. In addition, according to the results of this literature review, the overall malfunction rate in the pediatric group was higher when comparing to the adult group. The majority of articles that investigated the pediatric population showed that the rate of the malfunction was 45% or higher with a maximal

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LIMITATIONS

The retrospective nature of the most of included studies leads to an inevitable selection bias.

The data retrieved were based on searching all available clinical databases and electronic records, but there remains the potential for operations that were falsely coded and therefore may have been missed from the analysis.

Only a few studies showed a complication rate for the analyzed procedures.

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CONCLUSION

The risk of shunt malfunction is highest during the first few months after placing a VP shunt. Many factors have a direct effect on shunt malfunction, among which VP shunt obstruction and shunt infection were the most common.

Mechanical malfunctions of VP shunt include proximal obstructions of the catheter tip, distal obstructions, disconnections, kinking, disruptions, displacement, and valve-malfunctions. Shunt malfunction was more frequent due to proximal or distal occlusion of the catheter rather than valve-related problems.

Shunt infection is the second frequent cause of VP shunt malfunction, and this complication is most often observed in young individuals. Despite continuous attempts to lower the incidence of shunt complications, such as improved sterile techniques, antibiotic-impregnated catheters, and programmable valves, VP shunt dysfunction remains a huge problem.

To ameliorate the results for VP shunt surgery and decrease the rate of dysfunction, few recommendations arise from the review. Firstly, the insertion of a proximal catheter to the anterior horn of the lateral

ventricle by the frontal approach is preferred. The use of navigation guidance could improve the accuracy of catheter placement with the proximal tip positioned at maximal proximity to the foramen of Monro. Secondly, the use of both antibiotic-impregnated and silver-coated shunts could decrease the rate of infections. But the medical staff should be aware that the risk increases for infection with more virulent organisms.

Thirdly, the experience of the surgeon performing the insertion plays a major role in decreasing the risk of complications. With more experience, the procedure will safer and maximally time efficient.

Lastly, meticulous closure of operation wound with adequate approximation, will prevent CSF leakage and decrease the risk for shunt infection.

Ongoing and future prospective researches related to shunt malfunction should focus on preventing the two main etiologies of shunt malfunctions that this review has pointed out to alleviate the frequent

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REFERENCES

1- Reddy GK, Bollam P, Caldito G. Long-term outcomes of ventriculoperitoneal shunt surgery in patients with hydrocephalus. World Neurosurg. 2014;81:404-10.

2- Ahmed NDevitt KSKeshet ISpicer JImrie KFeldman L: A systematic review of the effects of resident duty hour restrictions in surgery: impact on resident wellness, training, and patient outcomes. Ann Surg 259:1041–10532014

3- Bondurant CPJimenez DF: Epidemiology of cerebrospinal fluid shunting. Pediatr Neurosurg 23:254–2591995

4- Al-Tamimi YZSinha PChumas PDCrimmins DDrake JKestle J: Ventriculoperitoneal shunt 30-day failure rate: a retrospective international cohort study. Neurosurgery 74:29–342014

5- Kestle JR, Holubkov R, Douglas Cochrane D, Kulkarni AV, Limbrick DD, Luerssen TG, Jerry Oakes W, Riva-Cambrin J, Rozzelle C, Simon TD, Walker ML, Wellons JC, Browd SR, Drake JM, Shannon CN, Tamber MS, Whitehead WE. Hydrocephalus Clinical Research Network. A new Hydrocephalus Clinical Research Network protocol to reduce cerebrospinal fluid shunt infection. J Neurosurg Pediatr. 2016; 17:391–396.

6- Jernigan SC, Berry JG, Graham DA, Goumnerova L. The comparative effectiveness of ventricular shunt placement versus endoscopic third ventriculostomy for initial treatment of hydrocephalus in infants. J Neurosurg Pediatr 2014; 13 (03) 295-300

7- Di Rocco C, Massimi L, Tamburrini G. Shunts vs endoscopic third ventriculostomy in infants: are there different types and/or rates of complications? A review. Childs Nerv Syst 2006; 22 (12) 1573-1589

8- Guillaume D, Menezes A. Hydrocephalus in Chiari malformation and other craniovertebral junction abnormalities. In: Cerebrospinal Fluid Disorders. Boca Raton, FL: CRC Press; 2009: 300-317 . Available at: http://www.crcnetbase.com/doi/abs/10.3109/9781420016284-18

9- Rabinstein AA, Jr MPK. Year Book of Neurology and Neurosurgery e-book. Elsevier Health Sciences; 2011

10- Programmlinie 4: Deutsch-Arabische Forschungspartnerschaft - Al Tawasul - DAAD - Deutscher Akademischer Austauschdienst. Available at: Shannon CN, Acakpo-Satchivi L, Kirby RS,

(34)

11- Beez T, Sarikaya-Seiwert S, Bellstädt L, Mühmer M, Steiger H-J. Role of ventriculoperitoneal shunt valve design in the treatment of pediatric hydrocephalus—a single center study of valve performance in the clinical setting. Childs Nerv Syst 2014; 30 (02) 293-297

12- Turhan T, Ersahin Y, Dinc M, Mutluer S. Cerebro-spinal fluid shunt revisions, importance of the symptoms and shunt structure. Turk Neurosurg 2011; 21 (01) 66-73

13- Simon TD, Butler J, Whitlock KB. , et al; Hydrocephalus Clinical Research Network. Risk factors for first cerebrospinal fluid shunt infection: findings from a multi-center prospective cohort study. J Pediatr 2014; 164 (06) 1462-8.e2

14- Notarianni C, Vannemreddy P, Caldito G. , et al. Congenital hydrocephalus and

ventriculoperitoneal shunts: influence of etiology and programmable shunts on revisions. J Neurosurg Pediatr 2009; 4 (06) 547-552

15- Kulkarni AV, Riva-Cambrin J, Butler J. , et al; Hydrocephalus Clinical Research Network. Outcomes of CSF shunting in children: comparison of Hydrocephalus Clinical Research Network cohort with historical controls: clinical article. J Neurosurg Pediatr 2013; 12 (04) 334-338

16- Riva-Cambrin J, Kestle JRW, Holubkov R. , et al; Hydrocephalus Clinical Research Network. Risk factors for shunt malfunction in pediatric hydrocephalus: a multicenter prospective cohort study. J Neurosurg Pediatr 2016; 17 (04) 382-390

17- Bakhsh A. CSF shunt complications in infants—an experience from Pakistan. Pediatr Neurosurg 2011; 47 (02) 93-98

18- Pople IK, Ettles D. The role of endoscopic choroid plexus coagulation in the management of hydrocephalus. Neurosurgery 1995; 36 (04) 698-701 ; discussion 701–702

19- Miranda P, Simal JA, Menor F, Plaza E, Conde R, Botella C. Initial proximal obstruction of ventriculoperitoneal shunt in patients with preterm-related posthaemorrhagic hydrocephalus. Pediatr Neurosurg 2011; 47 (02) 88-92

20- Putnam TJ. Treatment of hydrocephalus by endoscopic coagulation of the choroid plexus— description of a new instrument and preliminary report of results. N Engl J Med 1934; 210: 1373-1376 .

21- Garber ST, Riva-Cambrin J, Bishop FS, Brockmeyer DL. Comparing fourth ventricle shunt survival after placement via stereotactic transtentorial and suboccipital approaches. J Neurosurg Pediatr 2013; 11 (06) 623-629

(35)

23- Warf BC. Comparison of endoscopic third ventriculostomy alone and combined with choroid plexus cauterization in infants younger than 1 year of age: a prospective study in 550 African children. J Neurosurg 2005; 103 (6, Suppl): 475-481

24- Yavuz C, Demırtas S, Calıskan A. , et al. Reasons, procedures, and outcomes in ventriculoatrial shunts: a single-center experience. Surg Neurol Int 2013. Ab; Available at:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589837/

25- Yu S, Bensard DD, Partrick DA, Petty JK, Karrer FM, Hendrickson RJ. Laparoscopic guidance or revision of ventriculoperitoneal shunts in children. JSLS 2006; 10 (01) 122-125

26- Hamdan AR. Ventriculoperitoneal shunt complications: a localstudy at Qena University Hospital: a retrospective study. Egypt J Neurosurg. 2018;33:8 Khan F, Rehman A, Shamim MS, Bari ME. Factors affecting ventriculoperitoneal shunt survival in adult patients. Surg. Neurol. Int. 2015;6:25. 27- Khan F, Shamim MS, Rehman A, Bari ME. Analysis of factors affecting ventriculoperitoneal

shunt survival in paediatric patients. Childs Nerv. Syst. 2013 May;29(5):791-802.

28- Barton SE, Campbell JW, Piatt JH Jr. Quality measures for the management of hydrocephalus: concepts, simulations, and preliminary field-testing. J Neurosurg Pediatr.2013;11:392–7. 29- Konstantelias AA, Vardakas KZ, Polyzos KA, Tansarli GS, Falagas ME.

Antimicrobial-impregnated and -coated shunt catheters for prevention of infections in patients with

hydrocephalus: a systematic review and meta-analysis. J Neurosurg. 2015; 122:1096–1112. 30- .Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux

PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6:e1000100.

31- Shannon CN, Acakpo-Satchivi L, Kirby RS, Franklin FA, Wellons JC. Ventriculoperitoneal shunt failure: an institutional review of 2-year survival rates. Childs Nerv Syst 2012; 28 (12) 2093-2099 32- Rinker EK, Williams TR, Myers DT. CSF shunt complications: what the abdominal imager needs

to know. Abdom Imaging. 2015;40(6):2030–40.

33- Tuli SDrake JLawless JWigg MLamberti-Pasculli M: Risk factors for repeated cerebrospinal shunt failures in pediatric patients with hydrocephalus. J Neurosurg 92:31–382000

(36)

35- Wright BLC, Lai JTF, Sinclair AJ. Cerebrospinal fluid and lumbar puncture: A practical review. J Neurol. 2012;259(8):1530–45.

36- Pisapia JM, Sinha S, Zarnow DM, Johnson MP, Heuer GG. Fetal ventriculomegaly: Diagnosis, treatment, and future directions. Child’s Nerv Syst. 2017;33(7):1113–23.

37- Rochette A, Malenfant Rancourt MP, Sola C, Prodhomme O, Saguintaah M, Schaub R, et al. Cerebrospinal fluid volume in neonates undergoing spinal anaesthesia: A descriptive magnetic resonance imaging study. Br J Anaesth [Internet]. 2016;117(2):214–9. Available from:

http://dx.doi.org/10.1093/bja/aew185

38- Yamada SM, Kitagawa R, Teramoto A. Relationship of the location of the ventricular catheter tip and function of the ventriculoperitoneal shunt. J Clin Neurosci [Internet]. 2013;20(1):99–101. Available from: http://dx.doi.org/10.1016/j.jocn.2012.01.041

39- Reddy GK, Bollam P, Caldito G. Ventriculoperitoneal shunt surgery and the risk of shunt infection in patients with hydrocephalus: Long-term single institution experience. World Neurosurg

[Internet]. 2012;78(1–2):155–63. Available from: http://dx.doi.org/10.1016/j.wneu.2011.10.034 40- Erps A, Roth J, Constantini S, Lerner-Geva L, Grisaru-Soen G. Risk factors and epidemiology of

pediatric ventriculoperitoneal shunt infection. Pediatr Int. 2018;60(12):1056–61. 41- Lee JK, Seok JY, Lee JH, Choi EH, Phi JH, Kim SK, et al. Incidence and risk factors of

ventriculoperitoneal shunt infections in children: A study of 333 consecutive shunts in 6 years. J Korean Med Sci. 2012;27(12):1563–8.

42- Simon TD, Whitlock KB, Riva-Cambrin J, Kestle JRW, Rosenfeld M, Dean JM, et al. Revision surgeries are associated with significant increased risk of subsequent cerebrospinal fluid shunt infection. Pediatr Infect Dis J. 2012;31(6):551–6.

43- Rinaldo L, Lanzino G, Elder BD. Predictors of distal malfunction after ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus and effect of general surgery involvement. Clin Neurol Neurosurg [Internet]. 2018;174(September):75–9. Available from:

https://doi.org/10.1016/j.clineuro.2018.09.009

44- Spirig, José M ; Frank, Melanie N ; Regli, Luca ; Stieglitz, Lennart HenningShunt-age related complications in adult patients with suspected shunt dysfunction . A recommended diagnostic workup Authors : * José M . Department of Neurosurgery , University of Zurich and University Hospital Zurich , 8091 Faculty of Medicine , University of Zürich Switzerland Correspondence should be addressed to : 2017;159:1421–8.

45- Stone JJ, Walker CT, Jacobson M, Phillips V, Silberstein HJ. Revision rate of pediatric

(37)

46- Andreasen TH, Holst AV, Lilja A, Andresen M, Bartek J, Eskesen V, et al. Valved or valveless ventriculoperitoneal shunting in the treatment of post-haemorrhagic hydrocephalus: a population-based consecutive cohort study. Acta Neurochir (Wien). 2016;158(2):261–70.

47- Ahmadvand S, Dayyani M, Etemadrezaie H, Ghorbanpour A, Zarei R, Shahriyari A, et al. Rate and Risk Factors of Early Ventriculoperitoneal Shunt Revision: A Five-Year Retrospective Analysis of a Referral Center. World Neurosurg [Internet]. 2020;134(November):e505–11. Available from: https://doi.org/10.1016/j.wneu.2019.10.108

48- Prusseit J, Simon M, Von Der Brelie C, Heep A, Molitor E, Völz S, et al. Epidemiology, prevention and management of ventriculoperitoneal shunt infections in children. Pediatr Neurosurg. 2009;45(5):325–36.

49- Hanak BW, Bonow RH, Harris CA, Browd SR. Cerebrospinal Fluid Shunting Complications in Children. Pediatr Neurosurg. 2017;52(6):381–400.

50- Kestle JR, Holubkov R, Douglas Cochrane D, Kulkarni AV, Limbrick DD, Luerssen TG, Jerry Oakes W, Riva-Cambrin J, Rozzelle C, Simon TD, Walker ML, Wellons JC, Browd SR, Drake JM, Shannon CN, Tamber MS, Whitehead WE. Hydrocephalus Clinical Research Network. A new Hydrocephalus Clinical Research Network protocol to reduce cerebrospinal fluid shunt infection. J Neurosurg Pediatr. 2016; 17:391–396.

51- Merkler AE, Parker WE, Santosh B, Kamel H, Unit TN, Brain FF, et al. The Rate of Complications after Ventriculoperitoneal Shunt SurgeryHHS Public Access. 2018;654–8. 52- Korinek AM, Fulla-Oller L, Boch AL, Golmard JL, Hadiji B, Puybasset L. Morbidity of

ventricular cerebrospinal fluid shunt surgery in adults: An 8-year study. Neurosurgery. 2011;68(4):985–94.

53- Saehle T, Farahmand D, Eide PK, Tisell M, Wikkelso C. A randomized controlled dual-center trial on shunt complications in idiopathic normal-pressure hydrocephalus treated with gradually

reduced or “fixed” pressure valve settings. J Neurosurg. 2014; 121:1257–1263. [PubMed: 25192478]

54- Reddy GK. Ventriculoperitoneal shunt surgery and the incidence of shunt revision in adult patients with hemorrhage-related hydrocephalus. Clin Neurol Neurosurg [Internet]. 2012;114(9):1211–6. Available from: http://dx.doi.org/10.1016/j.clineuro.2012.02.050

55- Bonow RH, Hanak BW, Browd SR. Hydrocephalus in Children. Princ Neurol Surg [Internet]. 2018 Jan 1 [cited 2020 Apr 15];133-147.e3. Available from:

(38)

56- Sullivan RM. The Relationship between Ventriculoperitoneal Shunts and Shunt Revisions versus Visual Complaints among Patients with Spina Bifida in the Arkansas Spina Bifida Research Project. 2012;

57- Dobran M, Nasi D, Mancini F, Gladi M, Polonara G, Marini A, et al. Relationship between the location of the ventricular catheter tip and the ventriculoperitoneal shunt malfunction. Clin Neurol Neurosurg [Internet]. 2018;175:50–3. Available from:

https://doi.org/10.1016/j.clineuro.2018.10.006

58- Paff M, Alexandru-Abrams D, Muhonen M, Loudon W. Ventriculoperitoneal shunt complications: A review. Interdiscip Neurosurg Adv Tech Case Manag. 2018;13(April):66–70.

59- Lind CRP, Tsai AMC, Law AJJ, Lau H, Muthiah K. Ventricular catheter trajectories from traditional shunt approaches: A morphometric study in adults with hydrocephalus. J Neurosurg. 2008;108(5):930–3.

Literature Review of Ventriculoperitoneal Shunt Dysfunction Rates and Risk factors