Hydrocephalus Association Award

Since 1989, the Hydrocephalus Association has been awarding the Resident’s Prize. This prize is awarded each year to the most promising hydrocephalus-related research paper presented by a neurosurgical resident at the Pediatric Section meeting of the American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS).

This year I was lucky enough win this prestigious award with the abstract titled “CRISPR/Cas9-Based Development of progressive hydrocephaly (prh) Rat Model of Hydrocephalus.” I would like to thank the Mangano/Goto lab for making this possible, and thanks to our collaborators who helped us with this amazing research.

Resident’s Prize

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:



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?

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.

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

Joint Pediatric Section of the AANS/CNS

“Genetic Characterization of the progressive hydrocephaly (prh) Mouse Mutant”
Shawn Vuong, June Goto, Rolf Stottmann, Kenneth Campbell, and Francesco Mangano

Hydrocephalus is the most common brain malformation found at birth. Although the surgical intervention can greatly ameliorate outcomes, currently there is no medical cure for this condition. In addition, about 30% of these cases have unknown etiology. In order to identify molecular mechanisms involved in congenital hydrocephalus development, we investigated the genetic mutation responsible for progressive hydrocephaly (prh) mouse mutant, which was isolated in a previous forward genetic screening for severe neonatal onset hydrocephalus phenotype in mice. We performed a whole-genome sequencing in the mutant mouse and found a single nucleotide mutation candidate within Ccdc39 (coiled-coil domain containing protein 39) gene, one of primary ciliary dyskinesia genes critical for motile cilia functions. Western blotting and cDNA sequencing analysis show that the mutation affects proper mRNA splicing of the Ccdc39 gene and results in loss of the protein to undetectable levels. In immunohistochemistry, we found Ccdc39 is highly expressed in choroid plexus epithelium cells in the developing wild type mouse brain, but is missing from that of prh mutant. Choroid plexus is the major cerebrospinal fluid production site and has transiently motile multi-cilia in neonatal period. The transmission electron microscopy study revealed microtubule structures of choroid plexus cilia axoneme is disrupted in the prh mutant mice. In vitro trancytosis assay using primary cultured mouse choroid plexus cells showed altered fluid transferring rate in the mutant derived cells. Together, these data indicate that loss of Ccdc39 may disrupt the motility of choroid plexus cilia in the developing brain and suggest the possible involvement of choroid plexus cilia in the development of congenital hydrocephalus.

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


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