Ann Marie Flannery, Catherine A. Mazzola, Paul Klimo Jr., Ann-Christine Duhaime, Lissa C. Baird, Mandeep S. Tamber, David D. Limbrick Jr., Dimitrios C. Nikas, Joanna Kemp, Alexander F. Post, Kurtis I. Auguste, Asim F. Choudhri, Laura S. Mitchell, and Debby Buffa
Catherine A. Mazzola, Asim F. Choudhri, Kurtis I. Auguste, David D. Limbrick Jr., Marta Rogido, Laura Mitchell, and Ann Marie Flannery
The objective of this systematic review and analysis was to answer the following question: What are the optimal treatment strategies for posthemorrhagic hydrocephalus (PHH) in premature infants?
Both the US National Library of Medicine and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words relevant to PHH. Two hundred thirteen abstracts were reviewed, after which 98 full-text publications that met inclusion criteria that had been determined a priori were selected and reviewed.
Following a review process and an evidentiary analysis, 68 full-text articles were accepted for the evidentiary table and 30 publications were rejected. The evidentiary table was assembled linking recommendations to strength of evidence (Classes I–III).
There are 7 recommendations for the management of PHH in infants. Three recommendations reached Level I strength, which represents the highest degree of clinical certainty. There were two Level II and two Level III recommendations for the management of PHH.
Recommendation Concerning Surgical Temporizing Measures: I. Ventricular access devices (VADs), external ventricular drains (EVDs), ventriculosubgaleal (VSG) shunts, or lumbar punctures (LPs) are treatment options in the management of PHH. Clinical judgment is required. Strength of Recommendation: Level II, moderate degree of clinical certainty.
Recommendation Concerning Surgical Temporizing Measures: II. The evidence demonstrates that VSG shunts reduce the need for daily CSF aspiration compared with VADs. Strength of Recommendation: Level II, moderate degree of clinical certainty.
Recommendation Concerning Routine Use of Serial Lumbar Puncture: The routine use of serial lumbar puncture is not recommended to reduce the need for shunt placement or to avoid the progression of hydrocephalus in premature infants. Strength of Recommendation: Level I, high clinical certainty.
Recommendation Concerning Nonsurgical Temporizing Agents: I. Intraventricular thrombolytic agents including tissue plasminogen activator (tPA), urokinase, or streptokinase are not recommended as methods to reduce the need for shunt placement in premature infants with PHH. Strength of Recommendation: Level I, high clinical certainty.
Recommendation Concerning Nonsurgical Temporizing Agents. II. Acetazolamide and furosemide are not recommended as methods to reduce the need for shunt placement in premature infants with PHH. Strength of Recommendation: Level I, high clinical certainty.
Recommendation Concerning Timing of Shunt Placement: There is insufficient evidence to recommend a specific weight or CSF parameter to direct the timing of shunt placement in premature infants with PHH. Clinical judgment is required. Strength of Recommendation: Level III, unclear clinical certainty.
Recommendation Concerning Endoscopic Third Ventriculostomy: There is insufficient evidence to recommend the use of endoscopic third ventriculostomy (ETV) in premature infants with posthemorrhagic hydrocephalus. Strength of Recommendation: Level III, unclear clinical certainty.
David D. Limbrick Jr., Lissa C. Baird, Paul Klimo Jr., Jay Riva-Cambrin, and Ann Marie Flannery
The objective of this systematic review was to examine the existing literature comparing CSF shunts and endoscopic third ventriculostomy (ETV) for the treatment of pediatric hydrocephalus and to make evidence-based recommendations regarding the selection of surgical technique for this condition.
Both the US National Library of Medicine and the Cochrane Database of Systematic Reviews were queried using MeSH headings and key words specifically chosen to identify published articles detailing the use of CSF shunts and ETV for the treatment of pediatric hydrocephalus. Articles meeting specific criteria that had been determined a priori were examined, and data were abstracted and compiled in evidentiary tables. These data were then analyzed by the Pediatric Hydrocephalus Systematic Review and Evidence-Based Guidelines Task Force to consider treatment recommendations based on the evidence.
Of the 122 articles identified using optimized search parameters, 52 were recalled for full-text review. One additional article, originally not retrieved in the search, was also reviewed. Fourteen articles met all study criteria and contained comparative data on CSF shunts and ETV. In total, 6 articles (1 Class II and 5 Class III) were accepted for inclusion in the evidentiary table; 8 articles were excluded for various reasons. The tabulated evidence supported the evaluation of CSF shunts versus ETV.
Cerebrospinal fluid shunts and ETV demonstrated equivalent outcomes in the clinical etiologies studied.
Recommendation: Both CSF shunts and ETV are options in the treatment of pediatric hydrocephalus. Strength of Recommendation: Level II, moderate clinical certainty.
Jacob K. Greenberg, Eric Milner, Chester K. Yarbrough, Kim Lipsey, Jay F. Piccirillo, Matthew D. Smyth, Tae Sung Park, and David D. Limbrick Jr.
Chiari malformation Type I (CM-I) is a common and often debilitating neurological disease. Efforts to improve treatment of CM-I are impeded by inconsistent and limited methods of evaluating clinical outcomes. To understand current approaches and lay a foundation for future research, the authors conducted a systematic review of the methods used in original published research articles to evaluate clinical outcomes in patients treated for CM-I.
The authors searched PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and Cochrane databases to identify publications between January 2003 and August 2013 that met the following criteria: 1) reported clinical outcomes in patients treated for CM-I; 2) were original research articles; 3) included at least 10 patients or, if a comparative study, at least 5 patients per group; and 4) were restricted to patients with CM-I.
Among the 74 papers meeting inclusion criteria, there was wide variation in the outcome methods used. However, all approaches were broadly grouped into 3 categories: 1) “gestalt” impression of overall symptomatic improvement (n = 45 papers); 2) postoperative change in specific signs or symptoms (n = 20); or 3) results of various standardized assessment scales (n = 22). Among standardized scales, 11 general function measures were used, compared with 6 disease-specific tools. Only 3 papers used scales validated in patients with CM-I. To facilitate a uniform comparison of these heterogeneous approaches, the authors appraised articles in multiple domains defined a priori as integral to reporting clinical outcomes in CM-I. Notably, only 7 articles incorporated patient-response instruments when reporting outcome, and only 22 articles explicitly assessed quality of life.
The methods used to evaluate clinical outcomes in CM-I are inconsistent and frequently not comparable, complicating efforts to analyze results across studies. Development, validation, and incorporation of a small number of disease-specific patient-based instruments will improve the quality of research and care of CM-I patients.
Dustin K. Ragan, Jonathon Cerqua, Tiffany Nash, Robert C. McKinstry, Joshua S. Shimony, Blaise V. Jones, Francesco T. Mangano, Scott K. Holland, Weihong Yuan, and David D. Limbrick Jr.
Assessment of ventricular size is essential in clinical management of hydrocephalus and other neurological disorders. At present, ventricular size is assessed using indices derived from the dimensions of the ventricles rather than the actual volumes. In a population of 22 children with congenital hydrocephalus and 22 controls, the authors evaluated the relationship between ventricular volume and linear indices in common use, such as the frontooccipital horn ratio, Evans' index, and the bicaudate index. Ventricular volume was measured on high-resolution anatomical MR images. The frontooccipital horn ratio was found to have a stronger correlation with both absolute and relative ventricular volume than other indices. Further analysis of the brain volumes found that congenital hydrocephalus produced a negligible decrease in the volume of the brain parenchyma.
John R. W. Kestle, Richard Holubkov, D. Douglas Cochrane, Abhaya V. Kulkarni, David D. Limbrick Jr., Thomas G. Luerssen, W. Jerry Oakes, Jay Riva-Cambrin, Curtis Rozzelle, Tamara D. Simon, Marion L. Walker, John C. Wellons III, Samuel R. Browd, James M. Drake, Chevis N. Shannon, Mandeep S. Tamber, William E. Whitehead, and The Hydrocephalus Clinical Research Network
In a previous report by the same research group (Kestle et al., 2011), compliance with an 11-step protocol was shown to reduce CSF shunt infection at Hydrocephalus Clinical Research Network (HCRN) centers (from 8.7% to 5.7%). Antibiotic-impregnated catheters (AICs) were not part of the protocol but were used off protocol by some surgeons. The authors therefore began using a new protocol that included AICs in an effort to reduce the infection rate further.
The new protocol was implemented at HCRN centers on January 1, 2012, for all shunt procedures (excluding external ventricular drains [EVDs], ventricular reservoirs, and subgaleal shunts). Procedures performed up to September 30, 2013, were included (21 months). Compliance with the protocol and outcome events up to March 30, 2014, were recorded. The definition of infection was unchanged from the authors' previous report.
A total of 1935 procedures were performed on 1670 patients at 8 HCRN centers. The overall infection rate was 6.0% (95% CI 5.1%–7.2%). Procedure-specific infection rates varied (insertion 5.0%, revision 5.4%, insertion after EVD 8.3%, and insertion after treatment of infection 12.6%). Full compliance with the protocol occurred in 77% of procedures. The infection rate was 5.0% after compliant procedures and 8.7% after noncompliant procedures (p = 0.005). The infection rate when using this new protocol (6.0%, 95% CI 5.1%–7.2%) was similar to the infection rate observed using the authors' old protocol (5.7%, 95% CI 4.6%–7.0%).
CSF shunt procedures performed in compliance with a new infection prevention protocol at HCRN centers had a lower infection rate than noncompliant procedures. Implementation of the new protocol (including AICs) was associated with a 6.0% infection rate, similar to the infection rate of 5.7% from the authors' previously reported protocol. Based on the current data, the role of AICs compared with other infection prevention measures is unclear.
Jay Riva-Cambrin, John R. W. Kestle, Richard Holubkov, Jerry Butler, Abhaya V. Kulkarni, James Drake, William E. Whitehead, John C. Wellons III, Chevis N. Shannon, Mandeep S. Tamber, David D. Limbrick Jr., Curtis Rozzelle, Samuel R. Browd, Tamara D. Simon, and The Hydrocephalus Clinical Research Network
The rate of CSF shunt failure remains unacceptably high. The Hydrocephalus Clinical Research Network (HCRN) conducted a comprehensive prospective observational study of hydrocephalus management, the aim of which was to isolate specific risk factors for shunt failure.
The study followed all first-time shunt insertions in children younger than 19 years at 6 HCRN centers. The HCRN Investigator Committee selected, a priori, 21 variables to be examined, including clinical, radiographic, and shunt design variables. Shunt failure was defined as shunt revision, subsequent endoscopic third ventriculostomy, or shunt infection. Important a priori–defined risk factors as well as those significant in univariate analyses were then tested for independence using multivariate Cox proportional hazard modeling.
A total of 1036 children underwent initial CSF shunt placement between April 2008 and December 2011. Of these, 344 patients experienced shunt failure, including 265 malfunctions and 79 infections. The mean and median length of follow-up for the entire cohort was 400 days and 264 days, respectively. The Cox model found that age younger than 6 months at first shunt placement (HR 1.6 [95% CI 1.1–2.1]), a cardiac comorbidity (HR 1.4 [95% CI 1.0–2.1]), and endoscopic placement (HR 1.9 [95% CI 1.2–2.9]) were independently associated with reduced shunt survival. The following had no independent associations with shunt survival: etiology, payer, center, valve design, valve programmability, the use of ultrasound or stereotactic guidance, and surgeon experience and volume.
This is the largest prospective study reported on children with CSF shunts for hydrocephalus. It confirms that a young age and the use of the endoscope are risk factors for first shunt failure and that valve type has no impact. A new risk factor—an existing cardiac comorbidity—was also associated with shunt failure.
Travis R. Ladner, Jacob K. Greenberg, Nicole Guerrero, Margaret A. Olsen, Chevis N. Shannon, Chester K. Yarbrough, Jay F. Piccirillo, Richard C. E. Anderson, Neil A. Feldstein, John C. Wellons III, Matthew D. Smyth, Tae Sung Park, and David D. Limbrick Jr.
Administrative billing data may facilitate large-scale assessments of treatment outcomes for pediatric Chiari malformation Type I (CM-I). Validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code algorithms for identifying CM-I surgery are critical prerequisites for such studies but are currently only available for adults. The objective of this study was to validate two ICD-9-CM code algorithms using hospital billing data to identify pediatric patients undergoing CM-I decompression surgery.
The authors retrospectively analyzed the validity of two ICD-9-CM code algorithms for identifying pediatric CM-I decompression surgery performed at 3 academic medical centers between 2001 and 2013. Algorithm 1 included any discharge diagnosis code of 348.4 (CM-I), as well as a procedure code of 01.24 (cranial decompression) or 03.09 (spinal decompression or laminectomy). Algorithm 2 restricted this group to the subset of patients with a primary discharge diagnosis of 348.4. The positive predictive value (PPV) and sensitivity of each algorithm were calculated.
Among 625 first-time admissions identified by Algorithm 1, the overall PPV for CM-I decompression was 92%. Among the 581 admissions identified by Algorithm 2, the PPV was 97%. The PPV for Algorithm 1 was lower in one center (84%) compared with the other centers (93%–94%), whereas the PPV of Algorithm 2 remained high (96%–98%) across all subgroups. The sensitivity of Algorithms 1 (91%) and 2 (89%) was very good and remained so across subgroups (82%–97%).
An ICD-9-CM algorithm requiring a primary diagnosis of CM-I has excellent PPV and very good sensitivity for identifying CM-I decompression surgery in pediatric patients. These results establish a basis for utilizing administrative billing data to assess pediatric CM-I treatment outcomes.
Jacob K. Greenberg, Margaret A. Olsen, Chester K. Yarbrough, Travis R. Ladner, Chevis N. Shannon, Jay F. Piccirillo, Richard C. E. Anderson, John C. Wellons III, Matthew D. Smyth, Tae Sung Park, and David D. Limbrick Jr.
Chiari malformation Type I (CM-I) is a common and often debilitating pediatric neurological disease. However, efforts to guide preoperative counseling and improve outcomes research are impeded by reliance on small, single-center studies. Consequently, the objective of this study was to investigate CM-I surgical outcomes using population-level administrative billing data.
The authors used Healthcare Cost and Utilization Project State Inpatient Databases (SID) to study pediatric patients undergoing surgical decompression for CM-I from 2004 to 2010 in California, Florida, and New York. They assessed the prevalence and influence of preoperative complex chronic conditions (CCC) among included patients. Outcomes included medical and surgical complications within 90 days of treatment. Multivariate logistic regression was used to identify risk factors for surgical complications.
A total of 936 pediatric CM-I surgeries were identified for the study period. Overall, 29.2% of patients were diagnosed with syringomyelia and 13.7% were diagnosed with scoliosis. Aside from syringomyelia and scoliosis, 30.3% of patients had at least 1 CCC, most commonly neuromuscular (15.2%) or congenital or genetic (8.4%) disease. Medical complications were uncommon, occurring in 2.6% of patients. By comparison, surgical complications were diagnosed in 12.7% of patients and typically included shunt-related complications (4.0%), meningitis (3.7%), and other neurosurgery-specific complications (7.4%). Major complications (e.g., stroke or myocardial infarction) occurred in 1.4% of patients. Among children with CCCs, only comorbid hydrocephalus was associated with a significantly increased risk of surgical complications (OR 4.5, 95% CI 2.5–8.1).
Approximately 1 in 8 pediatric CM-I patients experienced a surgical complication, whereas medical complications were rare. Although CCCs were common in pediatric CM-I patients, only hydrocephalus was independently associated with increased risk of surgical events. These results may inform patient counseling and guide future research efforts.
Francesco T. Mangano, Mekibib Altaye, Robert C. McKinstry, Joshua S. Shimony, Stephanie K. Powell, Jannel M. Phillips, Holly Barnard, David D. Limbrick Jr., Scott K. Holland, Blaise V. Jones, Jonathan Dodd, Sarah Simpson, Deanna Mercer, Akila Rajagopal, Sarah Bidwell, and Weihong Yuan
The purpose of this study was to investigate white matter (WM) structural abnormalities using diffusion tensor imaging (DTI) in children with hydrocephalus before CSF diversionary surgery (including ventriculoperitoneal shunt insertion and endoscopic third ventriculostomy) and during the course of recovery after surgery in association with neuropsychological and behavioral outcome.
This prospective study included 54 pediatric patients with congenital hydrocephalus (21 female, 33 male; age range 0.03–194.5 months) who underwent surgery and 64 normal controls (30 female, 34 male; age range 0.30–197.75 months). DTI and neurodevelopmental outcome data were collected once in the control group and 3 times (preoperatively and at 3 and 12 months postoperatively) in the patients with hydrocephalus. DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were extracted from the genu of the corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). Group analysis was performed first cross-sectionally to quantify DTI abnormalities at 3 time points by comparing the data obtained in the hydrocephalus group for each of the 3 time points to data obtained in the controls. Longitudinal comparisons were conducted pairwise between different time points in patients whose data were acquired at multiple time points. Neurodevelopmental data were collected and analyzed using the Adaptive Behavior Assessment System, Second Edition, and the Bayley Scales of Infant Development, Third Edition. Correlation analyses were performed between DTI and behavioral measures.
Significant DTI abnormalities were found in the hydrocephalus patients in both the gCC (lower FA and higher MD, AD, and RD) and the PLIC (higher FA, lower AD and RD) before surgery. The DTI measures in the gCC remained mostly abnormal at 3 and 12 months after surgery. The DTI abnormalities in the PLIC were significant in FA and AD at 3 months after surgery but did not persist when tested at 12 months after surgery. Significant longitudinal DTI changes in the patients with hydrocephalus were found in the gCC when findings at 3 and 12 months after surgery were compared. In the PLIC, trend-level longitudinal changes were observed between preoperative findings and 3-month postoperative findings, as well as between 3- and 12-month postoperative findings. Significant correlation between DTI and developmental outcome was found at all 3 time points. Notably, a significant correlation was found between DTI in the PLIC at 3 months after surgery and developmental outcome at 12 months after surgery.
The data showed significant WM abnormality based on DTI in both the gCC and the PLIC in patients with congenital hydrocephalus before surgery, and the abnormalities persisted in both the gCC and the PLIC at 3 months after surgery. The DTI values remained significantly abnormal in the gCC at 12 months after surgery. Longitudinal analysis showed signs of recovery in both WM structures between different time points. Combined with the significant correlation found between DTI and neuropsychological measures, the findings of this study suggest that DTI can serve as a sensitive imaging biomarker for underlying neuroanatomical changes and postsurgical developmental outcome and even as a predictor for future outcomes.