
Hydrocephalus is a condition where too much cerebrospinal fluid (CSF) builds up in the brain. It’s a big problem for both patients and doctors. Usually, a ventriculoperitoneal (VP) shunt is put in to get rid of the extra CSF. But, shunts often need to be changed, leading to a search for better ways to treat it. Explore amazing alternatives to a shunt for hydrocephalus. Learn about successful ETV procedures and vital tips for better brain health.
We look into new ways to treat hydrocephalus and shunt alternatives that might help patients more. The healthcare world is always looking for new ideas. Knowing about these options is very important.
Key Takeaways
- Understanding hydrocephalus and its traditional treatment options.
- Exploring the need for alternative treatments to VP shunts.
- Reviewing the latest research on hydrocephalus management.
- Identifying possible shunt alternatives.
- Considering the future of hydrocephalus treatment.
Understanding Hydrocephalus and Its Challenges
Hydrocephalus is a complex brain condition affecting millions. It’s hard to diagnose and treat. It happens when too much cerebrospinal fluid (CSF) builds up in the brain, causing pressure.
What is Hydrocephalus?

Hydrocephalus is when the brain’s CSF balance is off. This imbalance makes the ventricles grow bigger.
Key aspects of hydrocephalus include:
- Accumulation of CSF in the brain’s ventricles
- Increased intracranial pressure
- Potential damage to brain tissue
- Varied symptoms depending on the type and severity
Common Causes of Hydrocephalus
Hydrocephalus can come from many things, like:
- Congenital conditions
- Traumatic brain injuries
- Infections such as meningitis
- Bleeding in the brain (hemorrhage)
- Tumors or cysts blocking CSF pathways
Knowing these causes helps doctors find better treatments.
How Cerebrospinal Fluid (CSF) Circulation Works
CSF is key to the brain’s health. It’s made in the ventricles and moves through the brain and spinal cord.
The CSF circulation process involves:
- Production of CSF by the choroid plexus
- Circulation through the ventricles and subarachnoid space
- Absorption into the bloodstream through arachnoid villi
Any problem in this process can cause hydrocephalus.
|
CSF Circulation Stage |
Description |
|---|---|
|
Production |
CSF is produced by the choroid plexus in the ventricles |
|
Circulation |
CSF circulates through the ventricular system and subarachnoid space |
|
Absorption |
CSF is absorbed into the bloodstream through arachnoid villi |
A leading neurosurgeon says, “Knowing how CSF moves is key to treating hydrocephalus.”
“Managing hydrocephalus needs a full plan, looking at the cause, symptoms, and the patient’s health.”
— Expert Neurosurgeon
Why Shunts Are the Standard Treatment for Hydrocephalus

Shunts have been the main treatment for hydrocephalus for many years. They help by draining extra fluid from the brain. We’ll look at why they’re so common, including their design, types, and the VP shunt procedure.
What is a Shunt and How Does It Work?
A shunt is a device that helps move cerebrospinal fluid (CSF) away from the brain. It has three parts: a catheter in the ventricle, a valve, and a distal catheter for fluid absorption.
The shunt creates a path for CSF to leave the brain, lowering pressure. The valve opens when pressure is too high, letting CSF flow and be absorbed elsewhere.
Types of Shunts Used in Hydrocephalus
There are different shunts for hydrocephalus, each with its own use. The most common is the ventriculoperitoneal (VP) shunt, which sends CSF to the peritoneal cavity.
Other shunts include ventriculoatrial (VA) and ventriculopleural (VPL) shunts. These drain into the heart and pleural space, respectively. The right shunt depends on the patient’s health and body.
The Ventriculoperitoneal (VP) Shunt Procedure
The VP shunt procedure is a common surgery for hydrocephalus. It involves a shunt that moves CSF from the ventricles to the peritoneal cavity for absorption.
The surgery starts with a scalp incision to reach the skull. A hole is drilled for the proximal catheter in the ventricle. The distal catheter is then placed in the abdomen.
The VP shunt procedure often helps lower brain pressure and ease symptoms. But, like any surgery, it comes with risks and complications that need careful management.
Common Complications That Make Alternatives to Shunts Necessary
Shunts used to treat hydrocephalus often face complications. These issues can greatly affect a patient’s life quality. Shunts have been the main treatment for hydrocephalus but come with many problems.
Shunt Malfunction and Failure Rates
Shunt malfunction is a big problem, needing quick medical help. Up to 50% of shunts fail within two years. This is a high failure rate.
Shunt failures can happen for many reasons. These include mechanical issues, blockages, or infections. Below is a table showing common reasons for shunt failures.
|
Cause |
Description |
Frequency |
|---|---|---|
|
Mechanical Failure |
Breakage or fracture of shunt components |
30% |
|
Blockage |
Obstruction of CSF flow within the shunt |
40% |
|
Infection |
Bacterial infection of the shunt system |
30% |
Infection and Other Complications
Infections are a big problem with shunts. These infections can cause serious issues like meningitis and even death. Prompt diagnosis and treatment are key to fighting shunt infections.
Long-term Management Challenges with Shunts
Long-term use of shunts for hydrocephalus comes with big challenges. Patients often need many surgeries for shunt changes. There’s always a risk of more problems. We must think about these issues when looking at treatment options for hydrocephalus.
Endoscopic Third Ventriculostomy (ETV)
Endoscopic Third Ventriculostomy (ETV) is a new way to treat hydrocephalus instead of traditional shunts. It creates a new path for cerebrospinal fluid (CSF) to flow. This means some patients might not need a shunt.
How ETV Works
ETV uses a neuroendoscope to see inside the brain. Surgeons make a small hole in the third ventricle. This lets CSF flow better and lowers pressure in the brain. It’s good for patients with blocked CSF flow.
Ideal Candidates for ETV
Not every patient with hydrocephalus can have ETV. The best candidates have blocked CSF flow. Doctors look at age, the reason for hydrocephalus, and past treatments to decide if ETV is right.
Success Rates and Outcomes
How well ETV works depends on the patient and their hydrocephalus cause. Some studies show it’s very effective for certain patients. But, it’s important to keep an eye on patients over time for any problems.
ETV vs. Shunt: Comparative Analysis
Choosing between ETV and a shunt depends on several things. ETV might lower the chance of shunt problems like infections. But, it’s not for every hydrocephalus case. Choosing the right treatment is key.
Choroid Plexus Cauterization (CPC)
Choroid Plexus Cauterization (CPC) is a new way to treat hydrocephalus. It’s seen as a good alternative to shunt treatments. This method involves stopping the brain from making too much cerebrospinal fluid (CSF).
The Procedure and Mechanism
CPC uses special tools to see and treat the choroid plexus. It uses heat to stop the brain from making CSF. This is helpful for those who can’t have shunts or have had problems with them.
“CPC is a natural way to handle hydrocephalus,” says a top neurosurgeon. “It stops CSF from building up, avoiding shunt problems.”
Combined ETV-CPC Approach
Using ETV and CPC together is a big step forward. ETV makes a new path for CSF to leave the brain. CPC stops the brain from making more CSF. This combo helps kids with hydrocephalus a lot.
This method works well for babies and young kids. It means fewer shunts and less chance of shunt problems.
Patient Selection Criteria
Choosing the right patients for CPC or ETV-CPC is key. The best candidates have certain types of hydrocephalus. They should not have done well with shunts or had many shunt failures.
- Patients with obstructive hydrocephalus
- Infants and young children
- Individuals with a history of shunt complications
Recovery and Follow-up Care
After the procedure, patients need to be watched for any problems. They have follow-up scans to see if the treatment worked. This helps check if CSF levels are okay.
Recovery times differ, but most stay in the hospital a few days. Long-term care is important to make sure the treatment lasts and to catch any new problems early.
Ventricular Access Devices and Reservoir Systems
Ventricular access devices, like Ommaya reservoirs, are key for patients needing frequent CSF sampling. They manage hydrocephalus without the need for repeated taps. This reduces the risk of complications from invasive procedures.
Ommaya Reservoirs and Similar Devices
Ommaya reservoirs are implanted under the scalp for easy access to the ventricular system. They’re great for administering medications or draining CSF to relieve pressure. Their design helps avoid infections and other complications.
These devices are vital for managing hydrocephalus, mainly for long-term CSF management. They offer a flexible treatment option tailored to each patient’s needs.
Applications in Specific Types of Hydrocephalus
Ventricular access devices help patients with certain hydrocephalus types, like communicating hydrocephalus. They’re also useful after a subarachnoid hemorrhage. Sampling CSF and monitoring pressure are key for treatment decisions.
In cases of meningitis or CSF infections, these devices allow for direct antibiotic treatment. This ensures effective infection treatment.
Maintenance Requirements
Keeping ventricular access devices clean is vital to avoid infections or malfunctions. Regular flushing and monitoring for infection signs are important. Patients and caregivers need to know how to care for these devices safely.
Regular check-ups with healthcare providers are also necessary. They ensure the device is working right and address any issues.
Neuroendoscopic Approaches Beyond ETV
Neuroendoscopy offers more than just Endoscopic Third Ventriculostomy (ETV) for managing hydrocephalus. It has become key in treating many neurosurgical conditions. This method is a less invasive alternative to traditional surgery.
Aqueductoplasty
Aqueductoplasty is a neuroendoscopic procedure that widens the cerebral aqueduct. This helps improve cerebrospinal fluid (CSF) flow. It’s useful when aqueductal stenosis causes hydrocephalus.
By improving CSF flow, aqueductoplasty might avoid the need for shunts in some patients.
Key benefits of aqueductoplasty include:
- Minimally invasive procedure
- Potential to avoid shunt placement
- Restoration of natural CSF flow
Septostomy
Septostomy is a neuroendoscopic method for treating hydrocephalus, mainly when CSF pathways are blocked. It creates a hole in the septum pellucidum for CSF to flow between ventricles. This can be a good alternative to complex shunt systems for certain hydrocephalus types.
Fenestration of Intraventricular Cysts
Fenestration of intraventricular cysts is a neuroendoscopic technique for managing ventricular cysts causing hydrocephalus. It involves making openings in these cysts to relieve pressure and restore CSF circulation. This method is beneficial for cysts hard to reach with traditional surgery.
Advantages of fenestration include:
- Reduced risk of infection compared to shunt placement
- Minimally invasive approach
- Potential for improved CSF dynamics
Technological Advancements in Neuroendoscopy
Neuroendoscopy is constantly evolving, thanks to technological advancements. High-definition imaging, better endoscope design, and advanced instruments are improving neurosurgeons’ capabilities. These advancements are making it possible to treat more conditions with neuroendoscopy.
As neuroendoscopy advances, we can look forward to more innovations in treating hydrocephalus and other neurosurgical conditions. New techniques and technologies will likely lead to better patient outcomes and more treatment options.
Lumbar-Peritoneal Shunts as an Alternative to VP Shunts
For those with hydrocephalus, lumbar-peritoneal (LP) shunts are a good choice. They drain cerebrospinal fluid (CSF) from the lower back to the belly. This way, they don’t need to go through the brain’s ventricles.
When LP Shunts Are Considered
LP shunts are best for certain hydrocephalus cases. This includes idiopathic intracranial hypertension or pseudotumor cerebri. They’re also good when getting to the brain’s ventricles is hard or risky.
Advantages Over Traditional VP Shunts
LP shunts have big pluses. They don’t carry the risks of putting a catheter in the brain, like infections or blockages. They’re also easier to put in for some patients, which can make surgery safer and quicker.
Key benefits of LP shunts include:
- Reduced risk of ventricular catheter obstruction
- Simplified implantation procedure in some cases
- Potential for fewer complications related to ventricular access
Limitations and Considerations
LP shunts aren’t for everyone. Choosing them depends on the hydrocephalus cause, patient’s body, and other health issues.
It’s important to think about the good and bad points and what each patient needs.
Patient Experience with LP Shunts
People with LP shunts often feel better, with less headaches and vision problems. But, they need regular check-ups and might need changes to their shunt.
Knowing what patients hope for and expect is key to taking good care of them. This helps get the best results for their health.
Medical Management of Hydrocephalus
Managing hydrocephalus medically involves several treatments to ease symptoms and improve outcomes. While surgery is often needed, medical care is key in some cases.
Acetazolamide and Other Medications
Acetazolamide is a main drug for hydrocephalus treatment. It reduces cerebrospinal fluid (CSF) production, easing pressure. It’s great for patients not ready for surgery or as a short-term fix until surgery.
Other drugs help with specific symptoms or complications. The right medication depends on the patient’s condition and hydrocephalus cause.
Temporary CSF Drainage Techniques
Temporary CSF drainage also helps patients with hydrocephalus. It removes CSF to lower intracranial pressure. It’s useful in urgent cases or to check if permanent solutions will work.
Limitations of Non-Surgical Approaches
Medical management has its limits. Drugs like acetazolamide can have side effects and may not work forever. Temporary drainage is not a lasting fix and might need to be done again. Choosing medical management should be a team decision with a healthcare provider.
Monitoring and Adjustment Protocols
Patients on medical management need regular checks to see how well treatment is working. This includes doctor visits, imaging, and tests. Changing treatment plans can improve results and reduce problems.
With careful medical management and monitoring, doctors can tailor treatments to meet each patient’s needs.
Emerging Experimental Treatments
New treatments are being developed to help hydrocephalus patients. These new methods aim to replace traditional shunt systems. They show great promise in managing this complex condition.
Gene Therapy Research
Gene therapy is a leading edge in treating hydrocephalus. It targets the genetic causes of the condition. Researchers aim to reduce or eliminate the need for shunting.
Studies are underway to find the best way to deliver gene therapy. Early results suggest significant promise for better patient outcomes.
Stem Cell Approaches
Stem cell therapy is also being researched for hydrocephalus treatment. Stem cells can differentiate into various cell types. This makes them a good option for repairing brain damage.
Researchers are looking into how stem cells can improve CSF dynamics. This could help reduce shunt complications.
Novel Drug Delivery Systems
New drug delivery systems are being developed for hydrocephalus. These systems aim for controlled release of drugs directly to the condition site. This could reduce side effects and improve treatment.
By avoiding traditional routes, these systems offer targeted treatment options.
Clinical Trials and Research Participation
Clinical trials are key in developing new hydrocephalus treatments. By joining these trials, patients get access to cutting-edge therapies. They also help advance medical knowledge.
We encourage patients and their families to consider clinical trials. This should be done under their healthcare provider’s guidance.
Managing Normal Pressure Hydrocephalus (NPH) Without Shunts
Managing NPH without shunts requires a detailed approach. It starts with understanding the diagnostic challenges. Normal Pressure Hydrocephalus is a condition where cerebrospinal fluid (CSF) builds up in the brain’s ventricles. This causes pressure on the brain, but the CSF pressure is normal, making diagnosis hard.
Diagnostic Challenges in NPH
Getting a correct NPH diagnosis is key to managing it well. The symptoms of NPH, like walking problems, memory loss, and bladder control issues, can be similar to other brain conditions. This makes it hard to diagnose. MRI and CT scans are important for spotting NPH and ruling out other conditions.
- Imaging Techniques: MRI and CT scans help see the ventricles and check CSF flow.
- Clinical Evaluation: It’s important to look at patient symptoms and medical history for a correct diagnosis.
- CSF Tap Test: A small CSF removal via lumbar puncture can show if symptoms get better with less CSF pressure.
Alternative Approaches for NPH Patients
For those not suited for shunt placement or who don’t want surgery, other options are considered. These might include:
- Medication Management: Some medicines can help manage symptoms, but they work differently for everyone.
- Rehabilitation Therapy: Physical, occupational, and speech therapy can boost functional abilities and quality of life.
- Lifestyle Modifications: Changing daily routines and activities can help manage symptoms and improve well-being.
When to Consider Non-Shunt Options for NPH
Non-shunt options are looked at when patients can’t have shunt surgery or when surgery fails. Some patients might also choose these options for personal reasons.
Patient Selection: Choosing the right patients for non-shunt treatments is very important. It involves a detailed look at their condition and how they might respond to different treatments.
Cognitive and Physical Therapy Interventions
Cognitive and physical therapy are key parts of NPH management without shunts. These therapies can improve brain function, movement, and overall quality of life.
- Cognitive Rehabilitation: Specialized cognitive training programs can enhance memory, attention, and executive function.
- Physical Therapy: Personalized physical therapy plans can improve mobility, balance, and gait, lowering the risk of falls.
Pediatric Considerations for Non-Shunt Treatments
Pediatric hydrocephalus needs special treatment plans. These plans must consider the child’s age, how it affects their growth, and the support from their family.
Age-Specific Treatment Approaches
Children with hydrocephalus need treatments that fit their age. For example, babies might do better with Endoscopic Third Ventriculostomy (ETV) or Choroid Plexus Cauterization (CPC).
Key considerations for age-specific treatment include:
- Assessing the child’s overall health and developmental stage
- Evaluating the cause and severity of hydrocephalus
- Considering the child’s growth and development after treatment
Developmental Outcomes with Different Treatments
The treatment choice greatly affects a child’s development. Non-shunt treatments aim to reduce complications and improve life quality.
For example, successful ETV can lessen the need for lifelong shunt use. This might lead to better development in cognitive and motor skills. Studies show that kids who get ETV or CPC can do better in school and with their movements.
Family Decision-Making Support
Families are key in deciding on treatment for pediatric hydrocephalus. They need full support and guidance.
Support mechanisms include:
- Clear communication about treatment options and possible results
- Emotional support for dealing with the diagnosis and treatment
- Access to resources for managing the condition at home and in school
School and Social Integration After Treatment
After treatment, it’s important for kids to go back to school and social activities. They might need extra help to do well in school and with friends.
Strategies for successful integration include:
- Creating individual education plans
- Providing counseling and support services
- Encouraging kids to join in extracurricular activities
Adult-Specific Alternative Treatments
Adult hydrocephalus treatment has grown to include new options beyond traditional shunts. We’re learning more about hydrocephalus in adults, leading to more personalized care.
Managing Acquired Hydrocephalus
Adults with acquired hydrocephalus face it due to trauma, hemorrhage, or infection. A detailed approach is needed, taking into account the cause, the patient’s health, and symptom severity. Endoscopic third ventriculostomy (ETV) is a promising alternative in some cases.
Ventricular access devices and reservoir systems also play a role. They allow for intermittent CSF drainage and monitoring, adding flexibility to treatment.
Post-Traumatic and Post-Hemorrhagic Cases
Hydrocephalus after brain injury or hemorrhage is complex. Treatment must address the hydrocephalus and the patient’s overall recovery. Rehabilitation is key in these cases, focusing on cognitive and physical recovery.
Choosing between ETV or lumbar-peritoneal shunts depends on the patient’s condition and hydrocephalus specifics.
Quality of Life Considerations
Quality of life is critical when choosing treatments for adult hydrocephalus. Alternative treatments aim to manage the condition and improve life quality. This includes avoiding complications and reducing medical interventions.
We collaborate with patients to create a treatment plan that meets their goals. This might involve improving cognitive function, reducing symptoms, or boosting overall well-being.
Vocational Rehabilitation Options
For many adults with hydrocephalus, work is a big concern. Vocational rehabilitation offers vital support. This includes workplace adjustments, job retraining, and other services to help patients stay productive.
By addressing the full spectrum of adult hydrocephalus needs, we provide care that supports medical, social, and professional goals.
Cost and Insurance Considerations for Shunt Alternatives
It’s important for patients and families with hydrocephalus to know about the costs of shunt alternatives. These treatments can be expensive, and understanding medical billing and insurance is key. This knowledge helps in making the best choices.
Comparative Costs of Different Procedures
The cost of shunt alternatives varies a lot. It depends on the procedure, the doctor, and where you live. For example, Endoscopic Third Ventriculostomy (ETV) and Choroid Plexus Cauterization (CPC) have different prices.
Several factors affect the cost:
- Hospital stay duration
- Surgical team fees
- Equipment and technology used
- Post-operative care requirements
Insurance Coverage for Alternative Treatments
Insurance for shunt alternatives can be tricky. It changes a lot between different insurance plans. Patients should check their insurance to see what’s covered.
Important things to consider include:
- Pre-approval requirements
- Out-of-pocket costs
- Coverage for follow-up care
- Any exclusions or limitations
Financial Assistance Programs
For many, the cost of shunt alternatives is too high. But, there are programs that help with the cost.
These programs offer:
- Patient advocacy services
- Grants and subsidies
- Sliding scale fees based on income
Long-term Economic Impact of Treatment Choices
The long-term cost of shunt alternatives is important. Even if some procedures are expensive upfront, they can save money in the long run. This is because they might need fewer shunt revisions and hospital visits.
When choosing treatments, think about the costs now and later. Consider savings from:
- Reduced hospital readmissions
- Fewer surgical interventions over time
- Improved quality of life and productivity
Knowing these factors helps patients make better choices. This can lower the total cost of their care.
How to Choose Between Shunt and Non-Shunt Options
Deciding between shunt and non-shunt treatments for hydrocephalus is complex. It depends on many factors. The best choice is often based on the patient’s condition, medical history, and needs.
Patient-Specific Factors to Consider
Several factors are important when choosing a treatment. These include:
- The cause of hydrocephalus
- The patient’s age and health
- The severity of symptoms
- Previous treatments or surgeries
Age is a big factor. Some treatments work better for kids, while others are better for adults. For example, Endoscopic Third Ventriculostomy (ETV) is often used for kids over one and some adults with hydrocephalus.
Consulting with Neurosurgical Teams
Talking to a neurosurgical team is key. They can explain the risks and benefits of each option. They use their knowledge and experience to help.
“Choosing between a shunt or another procedure should be after a thorough evaluation. It’s important to discuss it with a neurosurgeon, considering the latest research and the patient’s situation.”
Questions to Ask Your Doctor
It’s important to talk openly with your healthcare providers. Here are some questions to ask:
- What are the possible complications of each treatment?
- How will the chosen treatment affect my daily life or my child’s growth?
- What are the long-term results for each option?
- Are there new treatments or clinical trials that might be relevant?
By thinking about these factors and talking to doctors, patients can make good choices about their hydrocephalus treatment.
Conclusion: The Future of Hydrocephalus Treatment
The future of treating hydrocephalus looks bright. Researchers are working hard on new treatments and better ways to manage the condition. Advances in neurosurgery, like endoscopic procedures and new drug systems, are making a big difference.
New treatments like gene therapy and stem cells could change the game. They aim to fix the root causes of hydrocephalus. This might mean fewer shunts are needed.
Shunt alternatives will keep being important in treating hydrocephalus. New tech and treatment plans will make care better and more tailored to each patient.
We’re dedicated to top-notch healthcare and support for patients worldwide. By exploring new treatments and shunt options, we can make life better for those with hydrocephalus.
FAQ
What is hydrocephalus and how is it typically treated?
Hydrocephalus is when too much cerebrospinal fluid (CSF) builds up in the brain. This causes pressure to rise. Doctors usually treat it by putting in a ventriculoperitoneal (VP) shunt to drain the fluid.
What are the common complications associated with shunts?
Shunts can malfunction, get infected, or need constant adjustments. This can lead to more surgeries and ongoing care issues.
What is Endoscopic Third Ventriculostomy (ETV) and how does it work?
ETV is a surgery that makes a new path for CSF to leave the brain. It avoids the need for a shunt. A small hole is made in the third ventricle to let CSF out.
Who are ideal candidates for ETV?
People with blocked hydrocephalus, like those with aqueductal stenosis, are best for ETV. This includes those with ventricular blockages.
What is Choroid Plexus Cauterization (CPC) and how is it used?
CPC is a procedure that stops the choroid plexus from making CSF. It’s often paired with ETV, mainly for kids.
What are ventricular access devices and reservoir systems used for?
These devices let doctors take CSF samples and give meds directly to the ventricles. They’re an alternative to shunts for some cases.
What is Normal Pressure Hydrocephalus (NPH) and how is it managed without shunts?
NPH has normal CSF pressure but can cause problems. It’s managed without shunts through therapy, like cognitive and physical exercises.
Are there any emerging experimental treatments for hydrocephalus?
Yes, new treatments include gene therapy, stem cells, and drug delivery systems. They’re being tested in trials to find new ways to treat hydrocephalus.
How do I choose between shunt and non-shunt options for hydrocephalus treatment?
Choosing depends on the cause of hydrocephalus, age, and health. Talking to a neurosurgical team is key to finding the right treatment.
What are the cost and insurance considerations for shunt alternatives?
Costs and insurance vary for shunt alternatives. There might be financial help to cover treatment costs.
What are the long-term economic impacts of choosing shunt alternatives?
Shunt alternatives can save money by avoiding repeated surgeries and hospital stays. This can have a big economic benefit over time.
How do shunt alternatives impact quality of life for patients with hydrocephalus?
Shunt alternatives can improve life by reducing complications and helping with brain and body functions. This can greatly enhance a patient’s quality of life.
References
National Center for Biotechnology Information. Evidence-Based Medical Insight. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC11310213/