Aspirin still unproven as therapy for curbing brain aneurysm growth

Cincinnati — Could an aspirin a day keep an aneurysm at bay?

That was the question asked by stroke researchers in the University of Cincinnati Department of Neurosurgery. The researchers reviewed the cases of 186 patients who had unruptured intracranial (brain) aneurysms that were being monitored for growth at Mayfield Brain & Spine.

They found a tiny difference between patients who took an aspirin daily and those who did not take any aspirin. Aneurysms in the group that took aspirin grew in 11.9% of patients (3 percent per year) while aneurysms in the non-aspirin group grew in 16.5% (4 percent per year). Growth was measured by brain scans.

“Although patients on a daily aspirin regimen demonstrated a lower rate of aneurysm growth, the difference was not statistically significant,” said Andrew Ringer, MD, a neurosurgeon with Mayfield Brain & Spine and the study’s principal investigator. “We need to conduct additional research that involves a larger number of patients from multiple centers.”

The research team is plans to explore additional data collected from thousands of patients treated by the Mayfield Clinic to see if this trend continues, Dr. Ringer said.

The poster is being displayed February 20-21 at the 2017 Annual Meeting of the American Association of Neurological Surgeons / Congress of Neurological Surgeons Joint Cerebrovascular Section in Houston.

A brain aneurysm is bulge on an artery wall that can rupture as it grows thinner and weaker, releasing blood into the space between the brain and the skull, a potentially catastrophic event called a subarachnoid hemorrhage. Of the 30,000 Americans who experience a ruptured brain aneurysm each year, according to the Brain Aneurysm Foundation, 15 percent of patients with a subarachnoid hemorrhage die before reaching the hospital, while 4 out of 7 who recover will have disabilities.

Dr. Ringer, a professor of neurosurgery, said that because the aspirin study was retrospective, the researchers could not be sure that patients were taking aspirin as prescribed. A prospective study in which patients are divided into closely monitored groups – those taking aspirin and those not taking aspirin – would provide greater clarity, Dr. Ringer said.

“It is in the public’s interest to find out whether an inexpensive and accessible drug can help keep small, non-threatening brain aneurysms from becoming larger, more dangerous aneurysms that require endovascular or surgical intervention,” Dr. Ringer said.

Additional co-investigators in the aspirin and aneurysm study are Christopher Carroll, MD, Ryan Tackla, MD, William Jeong, MD, Shawn Vuong, and Joseph Serrone, MD.

The study received no internal or external funding. The investigators stated no conflicts of interest.

 

Originally published from:

https://www.mayfieldclinic.com/MC_PR/PR_17Feb20.htm

 

Questioning the classical flow of CSF

Data has already been adding up which clarifies the classic model of CSF flow that experts rely on, is not correct.  In almost all modern neuroscience literature, since the original work on hydrocephalus by Dr. Dandy, Dr. Blackfin, and Dr. Cushing, CSF is made by the choroid plexus.   Then CSF flows through the lateral ventricles into the foramen of Monroe, into the third ventricle, through the aqueduct of Sylvius, and into the fourth ventricle where it exits the ventricular system through the foramen of Magendie or Lushka into the cerebral subarachnoid space.  Then the CSF bathes the brain or spinal cord but eventually gets absorbed mostly in the arachnoid granulations, which was originally questioned by Dr. Dandy (2-Dandy) or a small amount through the olfactory lymphatic pathway. (1-Oreskovic)

This is the classical pathway which is still used today to formulate theories on how acute hydrocephalus, NPH, low-pressure hydrocephalus (3-Smalley), pseduotumor cerebri, and other CSF flow abnormalities happen.

However, a lab group in Croatia is strongly questioning the classical pathway, and for good reason.(1-Oreskovic). There group has found:

  1. Upright position creates a sub-atmospheric pressure environment intracranially, and a significantly increased pressure region in the lumbar cistern.  Given the physics of fluid dynamics, shouldn’t normal flow go from the lumbar cistern to the head? (4-Klarica)
  2. Acute hydrocephalus created by sudden blockage of the aqueduct of Sylvius or kaolin injection into the cisterna magna does not lead to increased pressure after 21 days.  How does ventriculomegaly form? (5-Mise)
  3. Heavy water in the ventricles never makes it out of the ventricular system, but is found in the blood stream. While marked-insulin does travel from the ventricles to the subarachnoid space, it probably travels from the subarachnoid space to the ventricles.  This suggests that water and thus CSF is not traveling in a unidirectional fashion as Dr. Dandy described, and macromolecules probably travel in both directions due to diffusion. (6-Bulat)

These experimental findings along with the recent discoveries of the brain lymphatic system, the glymphatic system, MRI phase contrast and time-SLIP studies of CSF flow in-vivo, and anecdotal evidence of patients with complete aqueduct blockages (by pineal region tumors) without acute hydrocephalus, brings a person to wonder, do we really have any understanding of CSF flow dynamics?

References:
1.Orešković D, Radoš M, Klarica M: New Concepts of Cerebrospinal Fluid Physiology and Development of Hydrocephalus. Pediatr Neurosurg:2016
2.Dandy WE: Experimental hydrocephalus. Ann Surg 2:345–351, 1919
3.Smalley ZS, Venable GT, Einhaus S: Low-Pressure Hydrocephalus in Children: a Case Series and Review of the Literature. Neurosurgery, 2017, pp 439–447
4.Klarica M, Radoš M, Erceg G, Petošić A, Jurjević I, Orešković D: The influence of body position on cerebrospinal fluid pressure gradient and movement in cats with normal and impaired craniospinal communication. PLoS ONE 9:e95229, 2014
5.Mise B, Klarica M, Seiwerth S, Bulat M: Experimental hydrocephalus and hydromyelia: a new insight in mechanism of their development. Acta Neurochir (Wien) 138:862–8– discussion 868–9, 1996
6.Bulat M, Lupret V, Orehković D, Klarica M: Transventricular and transpial absorption of cerebrospinal fluid into cerebral microvessels. Coll Antropol 32 Suppl 1:43–50, 2008

Application of emerging technologies to improve access to ischemic stroke care

Neurosurg Focus. 2017 Apr;42(4):E8. doi: 10.3171/2017.1.FOCUS16520.
Application of emerging technologies to improve access to ischemic stroke care.

Vuong SM, Carroll CP, Tackla RD, Jeong WJ, Ringer AJ.

Abstract
During the past 20 years, the traditional supportive treatment for stroke has been radically transformed by advances in catheter technologies and a cohort of prominent randomized controlled trials that unequivocally demonstrated significant improvement in stroke outcomes with timely endovascular intervention. However, substantial limitations to treatment remain, among the most important being timely access to care. Nonetheless, stroke care has continued its evolution by incorporating technological advances from various fields that can further reduce patients’ morbidity and mortality. In this paper the authors discuss the importance of emerging technologies-mobile stroke treatment units, telemedicine, and robotically assisted angiography-as future tools for expanding access to the diagnosis and treatment of acute ischemic stroke.

PMID: 28366070 DOI: 10.3171/2017.1.FOCUS16520

Vascular Diseases of the Spinal Cord: Infarction, Hemorrhage, and Venous Congestive Myelopathy

Abstract

Vascular pathologies of the spinal cord are rare and often overlooked. This article presents clinical and imaging approaches to the diagnosis and management of spinal vascular conditions most commonly encountered in clinical practice. Ischemia, infarction, hemorrhage, aneurysms, and vascular malformations of the spine and spinal cord are discussed. Pathophysiologic mechanisms, clinical classification schemes, clinical presentations, imaging findings, and treatment modalities are considered. Recent advances in genetic and syndromic vascular pathologies of the spinal cord are also discussed. Clinically relevant spinal vascular anatomy is reviewed in detail.

PMID: 27616317

Selective Digestive Decontamination (SDD) – The ICU Book

Lately I’ve been reading The ICU Book by Paul L. Marino.  Everyone in crticial care recommmends this book as standard reading for interns and junior residents, and I have to say it has been quite the read so far.

One of the articles in Marino’s book that has really stuck out to me has to do with selective digestive decontamination (SDD). Marino explains that in the presence of severe chronic illness, the G.I. tract becomes populated with more pathogenic organisms capable of causing invasive infections. He quotes one study that showed that hospitalized patients are often colonized with pathogenic organisms in the G.I. tract most notably aerobic gram-negative bacilli like Pseudomonas. This paper noted that the change in microflora is not environmentally driven, however it is directly related to the severity of illness in ICU patients. Marino recommends selective digestive decontamination for all ICU patients.

One example of this regimen includes a three-step decontamination process.

1. Oral cavity: a paste containing 2% polymyxin, 2% tobramycin, and 2% amphotericin to be applied inside the mouth with a gloved finger every 6 hours.

2. G.I. tract: 10 ml solution containing 100 mg polymyxin, 80 mg tobramycin, and 500 mg amphotericin and given via nasogastric tube every 6 hours.

3. Systemic: intravenous cefuroxime, 1.5 g given every 8 hours for the 1st 4 days of this therapy

Multiple years of randomized controlled trials have shown that ICU acquired infections are dramatically reduced with this kind of regimen. In one study that Marino quotes all 3 types of infections common in ICUs–pneumonia, urinary tract infections, and septicemia septicemia from vascular catheters–were significantly less frequent in patients who received selective digestive decontamination. Many clinical trials are showing a combined 40% relative reduction in the frequency of acquired infections in the ICU.

Marino mentions that over 20 years of experience with selective digestive decontamination and numerous reports of its efficacy clearly show the benefits related to selective digestive decontamination. However there continues to be a debate over the merits of this practice. Marino states two concerns that feed this debate. First the impact of SDD on mortality and also the possibility of the emergence of antibiotic resistant organisms. Marino points out that studies that support the relative reduction in mortality in ICU patients that have received selective digestive decontamination and also he points to studies that show no evidence of antibiotic resistance with use of a standard selective digestive decontamination regimen.

So the question is why don’t hospitals use this regimen in the ICU? I cannot speak for all hospitals, however I can speak for the UC Health. In our ICU we do not use a selective digestive decontamination regimen. I’ve questioned the fellows about this practice, and I usually receive an answer dealing with the concern of the emergence of antibiotic resistant organisms. When I explained that this was a huge part of Dr. Marino’s ICU book the fellows question the studies stating that most of these are over 10 years old. This prompted me to look again at the current data to see if SDD is still the huge benefit that Dr. Marino felt that it once was.

I found an article in the Expert Opinion of Pharmacotherapy, a metanalysis from this year which included 65 randomized controlled trials with over 15,000 enrolled patients, over a 25 year period.  This article concluded:

From an objective, and strictly evidence-based, perspective we conclude that SDD is recommended because there is level 1 evidence to support its use. Moreover, intensivists should be aware that SDD is a life-saving strategy: only 18 patients need to receive the full protocol of SDD to save one life. This makes the ethics of withholding SDD highly questionable.

This was incredibly shocking to me, because I felt that I have stumbled upon something in medicine with evidence so clear and for such a long term period that there seems to be absolutely no debate in the clinical literature.  With evidence this clear and strong, why isn’t SDD a routine in ICUs across the country? Are physicians really that set in their ways?

 

References:

Marino, Paul L. The ICU Book. 2007. Third Ed. Chapter 4 pg 63-80.

Silvestri L, van Saene HK, Petros AJ. Selective digestive tract decontamination in critically ill patients. Expert Opin Pharmacother. 2012 Jun;13(8):1113-29. Epub 2012 Apr 25.

Trust in the White Coat

Medical culture is a weird yet powerful force that bonds together those who practice medicine.  From the SOB in bed 2 to the frequent-flyer out in the waiting room, the connection that we get by speaking our medical lingo brings out a special bond  of the medical culture.  Its a large, sub-culture, and like many sub-cultures we have our different rules and lingo.  I would even argue that within our large medical sub-culture we have many many different smaller ones inside that.  Nurses, techs, doctors, etc.  And even among the doctors their tends to be this imaginary dividing line between specialties.

As a new resident, I’ve found it odd that the same day I’ve earned my long white coat, was also the same day the culture around me changed to the point where it was considered a “newbie” move to wear the long white coat around.  I was quickly made fun of for wanting to flaunt around the fact that now I was actually an MD.  It was a very odd feeling.

However, I have stood my ground, and continued to wear the long white coat despite what my fellow residents say.  While I admit, a large part of wearing the coat is for the extra pockets, I do enjoy the fact that it took me many years to earn it, and I do see it as a sense of pride.  But more-so, it turns out in the literature that the long white coat is actually a non-verbal way of instilling confidence, trust, empathy, and establishing a good doctor patient relationship. For proof please see the references below.

References:

http://www.ncbi.nlm.nih.gov/pubmed/22445730

http://www.ncbi.nlm.nih.gov/pubmed/16546951

http://www.ncbi.nlm.nih.gov/pubmed/18286342

http://www.ncbi.nlm.nih.gov/pubmed/16271913

http://www.ncbi.nlm.nih.gov/pubmed/20095290

http://www.ncbi.nlm.nih.gov/pubmed/2016013