Impact of Hydrocephalus

Title: Inpatient healthcare burden and variables influencing hydrocephalus-related admissions across the lifespan

Publication: Published in Journal of Neurosurgery in December 2022

Principal Investigators: Mark Luciano MD, PhD and Abhay Moghekar, MBBS

Summary: This study analyzed hospital costs and patient characteristics for hydrocephalus-related admissions in the US. In 2019, there were nearly 37,000 admissions related to hydrocephalus shunts, costing over $2.06 billion in total. Initial shunt placements made up over half of these admissions and accounted for nearly 60% of the total cost. Admissions for shunt infections requiring revision had the highest costs and longest hospital stays. Patients admitted in the first month of life had significantly higher costs and longer stays compared to other age groups. Overall, these findings highlight the substantial financial impact and diverse demographic patterns of hydrocephalus treatment across different age groups in the US healthcare system.

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Title: The clinical spectrum of hydrocephalus in adults: report of the first 517 patients of the Adult Hydrocephalus Clinical Research Network registry

Publication: Published in Journal of Neurosurgery in May 2019

Principal Investigator: Michael Williams, MD

Summary: This study examined 517 adults enrolled in the Adult Hydrocephalus Clinical Research Network (AHCRN) over two years, focusing on four types of hydrocephalus: those with a history from childhood (transition), unrecognized congenital cases, acquired cases due to other health issues, and suspected idiopathic normal pressure hydrocephalus (iNPH) in older adults. Most patients were untreated at the time of enrollment. Those with suspected iNPH showed the poorest cognitive and physical performance, while those with unrecognized congenital hydrocephalus fared the best. The study highlights the diverse impact of hydrocephalus on adults, with implications for diagnosis and treatment decisions across different patient groups. Future research aims to improve outcomes and quality of life for all types of adult hydrocephalus.

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iNPH Review Papers

Title: Current Update on Treatment Strategies for Idiopathic Normal Pressure Hydrocephalus

Publication: Published in Current Treatment Options in Neurology in December 2019

Principal Investigators: Mark Hamilton, MDCM

Summary: This review discusses the latest ways to diagnose and treat iNPH, highlighting improved surgical outcomes. In the past, results from iNPH surgery varied widely, but recent advances and standardized guidelines have led to much better success rates, with 73% to 96% of patients experiencing positive outcomes. Proper evaluation, selecting the right patients, and modern surgical techniques can help patients return to their normal activities. Team-based rehabilitation after surgery can further enhance recovery.

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Title: Idiopathic Normal Pressure Hydrocephalus

Publication: Published in Cerebrospinal Fluid Disorders in November 2018

Principal Investigators: Albert Isaacs, MD, Mark Hamilton, MDCM, & Michael Williams, MD

Summary: Hydrocephalus is a condition where excess cerebrospinal fluid (CSF) accumulates in the brain, typically due to an imbalance between CSF production and absorption. While it often causes increased pressure in the brain, some cases involve normal pressure. This form, known as normal pressure hydrocephalus (NPH), can result from events like trauma or infection. When NPH occurs without a known cause, it’s called idiopathic normal pressure hydrocephalus (iNPH), which is most common in adults over 65. iNPH is marked by difficulties in walking, memory problems, and loss of bladder control. This review discusses various aspects of iNPH, including its history, epidemiology, pathophysiology, risk factors, diagnostic criteria, neuroimaging, and treatments.

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Title: Characteristics of shunt failure in 38,095 adult shunt insertion surgeries: a systematic review and meta-analysis

Publication: Published in Neurosurgical Focus in April 2023

Principal Investigators: Sean Nagel, MD and Mark Hamilton, MDCM

Summary: In adults with hydrocephalus, a shunt is often used to drain the fluid. However, these shunts often fail, leading to repeated surgeries, patient suffering, and increased medical costs. While we know a lot about shunt failures in children, there’s less information about adults. A review of existing studies found that about 17% of shunts fail, with failure rates increasing the longer the shunt is in place—up to 32% after two years. The most common reasons for failure are blockages and infections, particularly at the end of the shunt. The review highlights the need for better ways to define, track, and prevent shunt failures in adults.

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Title: Placebo-controlled effectiveness of idiopathic normal pressure hydrocephalus shunting: a randomized pilot trial

Publication: Published in Neurosurgery in March 2023

Principal Investigator: Mark Luciano, MD, PhD

Summary: Shunt surgery, which drains excess fluid in the brain, has shown benefits in 60% to 70% of idiopathic normal pressure hydrocephalus (iNPH) patients, but more rigorous trials are needed to confirm its effectiveness. In a recent pilot study, researchers tested the effectiveness of shunt surgery by comparing patients with open shunts to those with shunts that were virtually turned off (placebo). Over four months, they measured walking speed, bladder control, daily activities, depression, and quality of life, keeping patients and assessors unaware of which group they were in. Researchers found that those with open shunts walked faster and had better bladder control than those in the placebo group, though the improvement in walking speed was not statistically significant. After four months, all patients’ shunts were activated, and their progress was followed for another eight months. The initial delay in activating the shunts did not affect their long-term benefits or increase complications. The study suggests that shunt surgery can improve walking speed and bladder symptoms in iNPH patients and that a larger placebo-controlled trial is feasible and safe.

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Title: Neuronavigation and Laparoscopy Guided Ventriculoperitoneal Shunt Insertion for the Treatment of Hydrocephalus

Publication: Published in Journal of visualized experiments: JoVE in October 2022

Principal Investigator: Mark Hamilton, MDCM

Summary: In adults with hydrocephalus, surgery to place a ventriculoperitoneal (VP) shunt—a tube that drains excess fluid from the brain—often fails due to infections or problems with tube placement. In this study, researchers aimed to improve VP shunt success rates by combining advanced surgical methods. They used electromagnetic navigation to precisely position the shunt’s starting tube and laparoscopy to guide the tube’s path into the abdomen. Specifically, the tube was placed through a small hole in the falciform ligament, avoiding areas that could block it. This approach, performed alongside measures to prevent infections, reduced overall shunt failure by 44% over seven years for 224 patients. The article includes a video that shows the surgery in action, highlighting how these techniques and collaborative efforts between neurosurgery and general surgery improve patient outcomes.

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Title: Reducing the risks of proximal and distal shunt failure in adult hydrocephalus: a shunt outcomes quality improvement study

Publication: Published in Journal of Neurosurgery in August 2021

Principal Investigator: Mark Hamilton, MDCM

Summary: In this study, researchers aimed to improve outcomes for adults undergoing ventriculoperitoneal (VP) shunt surgery, a common treatment for hydrocephalus, by combining advanced surgical techniques with infection prevention measures. They compared patients who underwent surgery before and after implementing a quality improvement study. Using neuro-navigation and laparoscopy techniques, alongside a shunt infection protocol, significantly reduced overall shunt failure rates from 37% to 14% at 1 year, with similar reductions at 2 and 3 years. Importantly, rates of shunt infections dropped to zero post-intervention, and distal catheter failures were also markedly reduced. This combined approach shows promise in enhancing the safety and effectiveness of VP shunt surgeries in adults with hydrocephalus.

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Evaluating Diagnostics & Treatment

Title: Safety and effectiveness of the assessment and treatment of idiopathic normal pressure hydrocephalus in the Adult Hydrocephalus Clinical Research Network

Publication: Published in Journal of Neurosurgery in March 2022

Principal Investigator: Michael Williams, MD

Summary: In this study, researchers followed suspected idiopathic normal pressure hydrocephalus (iNPH) patients treated at five Adult Hydrocephalus Clinical Research Network (AHCRN) medical centers for one year after shunt surgery. They evaluated 570 patients, with 424 undergoing initial fluid drainage tests. Of these, 193 patients underwent shunt surgery. Those who were shunted showed significant improvements in walking speed, cognitive function, bladder control, mood, and overall daily activities. Additionally, 91% of shunted patients had no complications, while 9% had complications, including 6% who experienced serious issues needing further surgery or hospital stays. Only 3% needed another surgery within 30 days. The researchers concluded that using recommended guidelines for evaluating and treating iNPH is safe and effective, resulting in significant patient improvements and low complication rates. They suggest using gait velocity (walking speed) as a standard measure to assess the success of treatments for iNPH. This study challenges previous claims that treating iNPH is harmful and supports the use of standardized treatment protocols.

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Title: Cognitive and gait outcomes after primary endoscopic third ventriculostomy in adults with chronic obstructive hydrocephalus

Publication: Published in Journal of Neurosurgery in September 2021

Principal Investigator: Tom Zwimpfer, MD

Summary: This study investigated how effective primary endoscopic third ventriculostomy (ETV) is for improving gait and cognition in adults with chronic obstructive hydrocephalus. The investigators evaluated 74 patients who underwent ETV, focusing on changes in walking speed and cognitive function before and after the procedure. In the short term (about 5 months after ETV), patients showed significant improvements in walking speed and slight gains in cognitive scores. These improvements were sustained in the long term (about 14 months after ETV), with further increases in both walking speed and cognitive function. Complications were minor, and most patients with congenital or acquired forms of hydrocephalus benefited from the procedure without worsening symptoms. This research supports ETV as a safe and effective treatment option for adults with chronic obstructive hydrocephalus.

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Title: Extended lumbar drainage in idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis of diagnostic test accuracy

Publication: Published in British Journal of Neurosurgery in July 2020

Principal Investigator: Richard Edwards, MD

Summary: This review analyzed studies on extended lumbar drainage (ELD) as a test for diagnosing iNPH. ELD is used to predict if patients will benefit from surgery to drain this fluid. However, findings from four small studies varied widely in accuracy. On average, ELD showed about 94% sensitivity (ability to detect iNPH) and 85% specificity (ability to rule out iNPH). Positive and negative predictive values, indicating how well ELD predicts outcomes, were both around 90%. More large-scale studies are needed to confirm ELD’s reliability in diagnosing iNPH and guiding treatment decisions effectively.

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Title: Standardized regression-based clinical change score cutoffs for normal pressure hydrocephalus

Publication: Published in BCM Neurology in April 2020

Principal Investigator: Abhay Moghekar, MBBS

Summary: In patients suspected of having NPH, temporary drainage CSF helps doctors assess if symptoms improve significantly. Researchers studied 323 patients over 60 years old who underwent CSF drainage and tested their walking speed, balance, and cognitive abilities before and after. They developed models to predict meaningful improvements in these tests, helping doctors distinguish real improvements from chance. The Timed Up & Go test was particularly reliable in predicting changes in walking speed and overall mobility. These findings provide a useful tool for doctors to better manage and treat NPH patients based on objective evidence of improvement.

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Biomarkers of iNPH

Title: Molecular Signatures of Normal Pressure Hydrocephalus: A Largescale Proteomic Analysis of Cerebrospinal Fluid

Publication*: Published in bioRxiv in March 2024

Principal Investigator: Abhay Moghekar, MBBS

Summary: Researchers conducted a detailed study of CSF in patients with iNPH, Alzheimer’s-related mild cognitive impairment, and healthy individuals. They discovered unique protein patterns in iNPH patients, including lower levels of proteins related to synapses and cell adhesion, and higher levels of inflammation markers. These findings suggest issues with the brain’s fluid flow and its lining. Additionally, similarities with proteins linked to congenital hydrocephalus hint at a possible shared cause. The study identified 13 proteins that could serve as diagnostic markers for iNPH, potentially leading to better diagnosis and understanding of the condition.

*This is a preprint. It has not yet been peer reviewed by a journal.

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Title: Neuronal pentraxin 2 correlates with neurodegeneration but not cognition in idiopathic normal pressure hydrocephalus (iNPH)

Publication: Published in Polish Journal of Neurology and Neurosurgery in February 2024

Principal Investigator: Abhay Moghekar, MBBS

Summary: Researchers wanted to see if a protein called Neuronal Pentraxin-2 (NPTX2), linked to brain function, could predict cognitive abilities in patients with iNPH and if it could indicate how well patients would respond to shunt surgery. The study included 354 iNPH patients who underwent CSF drainage. Researchers measured the levels of NPTX2 and other markers in the CSF and compared these with patients’ cognitive and physical abilities before and after surgery. The study found that while NPTX2 levels were related to some markers of brain degeneration, they did not correlate with cognitive abilities or daily functioning in iNPH patients. Additionally, NPTX2 levels could not predict short-term or long-term improvements after surgery. The results suggest that the protein NPTX2, despite being linked to neurodegeneration, is not a useful marker for predicting cognitive outcomes or the effectiveness of surgical treatment in iNPH patients. This suggests that synaptic degeneration might not be a central part of iNPH’s underlying mechanisms.

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Title: CSF Biomarkers Predict Gait Outcomes in Idiopathic Normal Pressure Hydrocephalus

Publication: Published in Neurology: Clinical Practice in April 2022

Principal Investigator: Abhay Moghekar, MBBS

Summary: Researchers studied whether specific markers in CSF could predict which patients with iNPH would benefit from shunt surgery. They tested 354 patients and found that lower levels of certain markers (NfL, pTau181, tTau, and Aβ1–40) were linked to better long-term walking outcomes after surgery. However, combining these markers with MRI results only slightly improved predictions for short-term improvements after a fluid drainage test. The findings suggest that these CSF biomarker levels can help identify patients who might benefit most from shunt surgery and may also highlight other underlying brain conditions in those who do not respond well.

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Title: Predicting Cognitive Improvement in Normal Pressure Hydrocephalus Patients Using Preoperative Neuropsychological Testing and Cerebrospinal Fluid Biomarkers

Publication: Published in Neurosurgery in October 2019

Principal Investigator: Guy McKhann II, MD

Summary: This study aimed to predict cognitive improvement in patients with NPH after ventriculoperitoneal shunting (VPS). Researchers followed 52 patients over approximately one year, conducting neuropsychological tests before and after lumbar drainage and shunting. The Rey Auditory Verbal Learning Test-L (RAVLT-L) showed significant cognitive improvement after both procedures, suggesting it could predict post-shunt improvement. Biopsies indicated patients with Aβ+ Tau+ had specific CSF biomarkers, but these were not directly linked to cognitive outcomes. The study recommends using RAVLT-L for preoperative evaluation and calls for larger studies to assess CSF biomarkers’ predictive value in NPH treatment.

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