Welcome side effects of the pandemic

• It is without a doubt that a crisis will bring the best of us, and this holds true especially when it comes to medical research. It is widely known that research advanced tremendously during the two World Wars. As they say necessity is the mother of all invention.
  
  
  We are just seeing a similar orgasm of research collaborations happening all around the globe at present. One look at this trials tracker will show that there are currently 548 registered  trials (as of 8th of April 2020) with 44 participating countries. China, the USA and Iran are the three countries participating in most trials perhaps due to self interest or realization of the opportunity at hand, followed predictably by Italy, Spain and France due to the tremendous impact of the pandemic on these countries. It would be a real waste for healthcare systems of these countries to treat so many patients and not learn from the clinical experience or produce significant amounts of data that will advance medical knowledge and treatment.
  
  
  If I counted correctly there are trials for 151 different modalities or regimes to be studied ranging from the use of oxygen to fancy remedies like recombinant Cytokine Gene-Derived Protein and anything in between, inclusive of traditional or non-conventional medical treatments. It is worth noting that this tracker does not list purely observational studies, studies of diagnostic tests, or studies of prognostic markers for these patients. So there are 151 ongoing trials of interventional measures or treatment regimes. Most of these regimes are studied in combination so the number of trials may be smaller than the one I quoted. 
  
  
  Predictably most modalities focus on treatment and the aftermath of suffering from the infection (e.g. rehabilitation) and sadly fewer on non pharmacological preventive measures. For example, anyone who follows the news and the W.H.O. proposals would be aware of the ambiguity and the endless discussions around a simple preventive measure such as wearing a mask when in public. There is currently only one trial focusing on the use of the N95 respirator. 
  
  
  The “happy side effect”of the pandemic is the rush of research it produced, that will hopefully be important for the future of medical research in general. It shows how the medical community in times of need can mobilise swiftly. Barriers can be broken and multicentre trials can be organised within a couple of months. Assuming that all the trials had due diligence procedures completed it is surprising how many steps have been overcome in a fraction of the usual required time. Ethics applications were completed, funding obtained, launching of data collection platforms and multicentre applications were carried out, staff training & allocation and onset of recruitment was completed in record time. Of course, the infrastructure was already there but necessity demonstrated how procedures that appear cumbersome and tedious were fast tracked. 
  
  
  Knowing how research is the Cinderella of medical practice one has to wonder whether during normal circumstances we are asking the right questions and if so why isn’t research the tip of the spear? It also demonstrates that the systems are ready and in place for future global trials. It is just willingness that is lacking. 
  
  
  Resources for COVID-19 related research trials:
  • WHO International Clinical Trials Registry Platform, 
  • European Clinical Trials Registry, 
  • clinicaltrials.gov, 
  • Chinese Clinical Trial Registry, 
  • German Clinical Trials registry, 
  • Japan Primary Registries Network, 
  • Iranian Clinical Trial Registry, and 
  • Australian & New Zealand Clinical Trials Registry

Do follow updates in Normal Pressure Hydrocephalus literature below:


https://www.readbyqxmd.com/keyword/13396

A new look at cerebrospinal fluid circulation

Response to Brinker T.

Fluids Barriers CNS. 2014. Andrew Tarnaris 2014 Sep 15 7:17 p.m.

Corresponding author:
Andrew Tarnaris University Hospitals Birmingham Foundation NHS Trust Department of Neurosurgery Queen Elizabeth Medical Centre, Birmingham B15 2TH, United Kingdom.
Email: andrewtarnaris@gmail.com

I have read with interest the review article by Brinker et al. titled "A new look at cerebrospinal fluid circulation" published in Fluids Barriers CNS, 2014 May. The authors discuss key developments regarding cerebral cerebrospinal fluid (CSF) circulation including of production and absorption touching particularly among others the Virchow-Robin space (VRS) circulation.

The significance of VRS in hydrocephalus in general has not been thus far well investigated [1]. Our group first attempted to examine the significance of VRS circulation in idiopathic normal pressure hydrocephalus (iNPH), and in particular investigate whether they could represent a surrogate imaging marker for coexisitng microvascular disease which is known to co-exist in a subset of patients with iNPH [2]. In that preliminary study we concluded that there may be a higher incidence of VRS in patients with iNPH, when compared with normal patients of similar age, however we could not prove with that initial study that there was any correlation with microvascular co-morbidities. We suggested that our data should be followed in a larger set of patients.

We thus followed with a second study that was first presented in Hydrocephalus 2012 in Kyoto Japan entitled “In vivo study of the relationship of CSF dynamics and Virchow-Robin spaces in idiopathic normal pressure hydrocephalus “ (1OS-A2-05). We presented data from 17 patients with a diagnosis of iNPH and correlated the frequency of VRS with physiological data from lumbar infusion studies. Lumbar infusion studies can give unique information about the state of CSF dynamics in an individual. In summary we noted a lower compensatory reserve being associated with more intense perivascular CSF absorption, that resulting in a decrease in global outflow resistance. In that larger study (data submitted elsewhere) we confirmed that the incidence of VRS does not differ in normal population with the same risk factors for microvascular disease and proposed that VRS in iNPH may have a different pathophysiological origin representing impaired CSF circulation [3].

We are glad that the concept of our previous work is now acknowledged in this excellent review and hope that other groups will investigate the role of VRS in iNPH or hydrocephalus in general with modern imaging or by employing other experimental models.

References
[1] Gideon P, Thomsen C, Gjerris F, Sørensen PS, Henriksen O. Increased self-diffusion of brain water in hydrocephalus measured by MR imaging. Acta Radiologica. 1994;35(6):514-9.
[2] Tarnaris A, Tamangani J, Fayeye O, Kombogiorgas D, Murphy H, Gan YC, et al. Virchow-Robin Spaces in Idiopathic Normal Pressure Hydrocephalus: A Surrogate Imaging Marker for Coexisting Microvascular Disease? Hydrocephalus.33-7.
[3] W.A. Mohamed, A. Tarnaris, H. Murphy, M. Csoznyka, Flint G. In vivo study of the relationship of CSF dynamics and Virchow – Robin spaces in idiopathic normal pressure hydrocephalus. Society of British Neurological Surgeons; 2012 October 2012; Leeds: British Journal of Neurosurgery; 2012. p. 596-629. PermalinkShare

A report from the inaugural meeting of the British Neurosurgical Trainee Research Collaborative held in the Royal College of Surgeons of England, 19 October 2012.

Br J Neurosurg. 2013 Jun;27(3):307-10. doi: 10.3109/02688697.2013.781122. Epub 2013 Mar 26. Kolias AG, Jones TL, Cowie CJ, Coulter IC, Afshari FT, Tarnaris A, Nelson RJ, Gray WP, Hutchinson PJ, Brennan PM; UK Neurosurgical Research Network; British Neurosurgical Trainee Research Collaborative. Source Division of Neurosurgery, Addenbrooke's Hospital & University of Cambridge , Cambridge , UK. Abstract Abstract Clinical research, which is essential for improving patient outcomes, is increasingly carried out in the context of networks established between multiple institutions. Research is also considered an important component of training curricula. The recent successful completion of a randomised trial (ROSSINI), which was led by general surgical trainees of the West Midlands Research Collaborative, has established the feasibility of trainee collaborative research networks. A research network for neurosurgical trainees in the UK and Ireland was, therefore, established following the meeting of the British Neurosurgical Trainee Association (BNTA) in Aberdeen on 19 April 2012. This BNTA initiative quickly gained the full support from the Society of British Neurological Surgeons and the UK Neurosurgical Research Network. The inaugural meeting of the British Neurosurgical Trainee Research Collaborative took place at the Royal College of Surgeons of England, London, on 19 October 2012. The purpose of this report is both to record progress to date and to promote this concept.

Future Neurosurgery...

Mr. Green, a successful venture capitalist in wireless communication, entered the famous Brainsterium.

He had developed a malignant brain tumor as confirmed by a non-excisional optical biopsy. His feelings were mixed. He had expected to undergo a gene therapy, but he was offered a classic tumor resection. His colleagues in life sciences invested heavily in gene therapy, so he expected to benefit out of it. He realized that none of them invested in image-guided surgery.

Thus, he felt that an obsolete technology would decide about his life. On the other hand, the Brainsterium had a brand name and an impeccable reputation to be the best.

His first impression upon entering the Brainsterium was surprisingly positive. He rather expected a terrible hospital smell, miserable patients being moved around, and a noisy crowd of visitors, as he had experienced while visiting a hospital the last time when his father had got a stroke.What he saw instead looked like a quiet high-tech lab. He headed towards the office of the chief neurosurgeon, Dr. Noki, who would explain to him the procedure and supervise the surgery. Supervise, not operate; this was the major difference that the Brainsterium offered to its patients.

‘‘It is you who decides what to keep in and what to remove from your brain. We just provide the right environment to do it’’ – started Dr. Noki.

Mr. Green looked surprised. Do-it-yourself neurosurgery? He had no idea about this market segment.

‘‘Your brain will be unlocked and you will be able to view its content, such as knowledge, skills 

and memories, and examine how they are being invaded by the tumor’’ – continued Dr. Noki.

‘‘This surgery has two contradictory goals. One is to destroy all tumorous cells completely and the 

other is to maximally preserve the functions of your brain. I will provide you with two extreme brain resection regions: the conservative region with the core tumor only, and the aggressive region that contains the core tumor along with all tumorous cells that have migrated away from it. You have to balance between them to plan your postoperative life. When all tumorous cells are completely removed, the chances of physical survival are higher. This is the best for your body, but not necessarily for your mind and career. Preserving maximally your brain functions sounds more  attractive but it puts your life at a higher risk.’’

Mr. Green suddenly visualized his brain as a financial asset and things became clear. As the exclusive owner of his brain and its content, he himself wanted to have a full control over this asset and decide about the associated risk.

‘‘Someone’s brain is much more valuable than his bank account’’ – he thought, ‘‘so why for decades 

has this been working differently?’’

He was more and more eager to understand this worth-investing technology. He once had run an R&D department before becoming a venture capitalist.

Dr. Noki provided more operational details. ‘‘You will be given access to our patients’ database and have permission to communicate with anyone who underwent this type of surgery. If you decide to proceed and accept our terms and conditions, you will be allowed to access all tutorials and simulators, and you can play back any previous surgery with, of course, no access to the brain contents of our patients.’’

‘‘In the next step’’– continued Dr. Noki –‘‘your brain will be unlocked by measuring its magnetic, electrical, chemical, and optical properties using a battery of techniques. They will produce the images of anatomy, vasculature, connectivity, function, pathology, and knowledge in your brain. If you are interested in technical details, refer to our tutorials. The extent of the tumor will be defined, and the conservative and aggressive resection regions prepared for you. You will be trained to understand the images employed to plan the resection. These images show tissue at the micron’s scale and at this resolution it is easy to distinguish normal from tumorous cells. The content of the resected brain region can be partly recovered. Your memories will be retrieved and saved on a disk. Play it later at home so that your brain will restore these memories in new locations. Remapping of the skills and knowledge is still at an experimental stage. At present, the content of the resected brain will be recorded and stored. We will acquire the knowledge distribution map of your brain later to find suitable locations for placing back the recovered content. There is a chance that some day, with the advancements in knowledge remapping and brain reconnection technologies, your skills and knowledge will be fully recovered. Finally, the tumor will be ablated with the collimated ultrasonic scalpel and removed without opening your skull. It will be dissolved and sucked out through the vasculature. All actions and operations will be controlled by our revolutionary surgical environment.’’ The introduction was over. Mr. Green was ready for this fascinating journey. He began it from the Resource Center ushered by a lion-robot. He was requested to put his fingers on the scanning plate and look into a camera to capture his biometrics. Mr. Green logged into the patients’ database and entered his personal wavelength. He had quite a broad band, which substantially accelerated operations.

First, he registered with the system and displayed the list of patients who underwent a similar procedure. There were several thousands of them. No mortality, no technical failure during surgery; neurological deficits were quite variable, however. Whom to ask? He entered his year and place of birth. There was a familiar name, Jack Case. They had been schoolmates in grade six before his family moved to the West Coast.

Mr. Green requested a videoconferencing session. He was lucky. Jack was in his garden and Mr. Green recognized his old friend. Jack had chosen the complete tumor removal 2 years back. He quit his job and was spending his days tendering his oceanside garden. Today Jack would opt differently. Mr. Green terminated the session and was led to the Brain Unlocking Center.

A pretty nurse with an east European accent welcomed him. He was asked to provide a detailed list of his skills and related knowledge. The questionnaire was quite boring but Mr. Green realized that it was critical for an accurate planning of his brain stimulation and knowledge mapping. Next, the nurse put a bulky helmet on his head. ‘‘This must be that famous BCC, Brainsterium’s collector and collimator – one of the key unfair advantages of the Brainsterium. How did they manage to design this three-in-one gadget able to acquire multi-modal data and to collimate myriad of energy sources dynamically providing a non-invasive access to any location in the brain at micron’s accuracy for stimulation and excision?’’ – wondered Mr. Green. While stimulated, he experienced unusual sensations.

He saw some strange visual effects, heard funny voices, smelled oriental plants, and had an impression 

he was flying while the angels were singing. ‘‘No, not yet’’ – he said. ‘‘This is just a knowledge mapping procedure.’’ He looked at his body tightly attached to the chair. His excitement rocketed when he entered the Brain Exploration Center It resembled a cyber cafe he had used to visit with his son a long time ago. Patients with helmets sitting in cubicles appeared playing games and navigating through 

some mazes. But everyone played seriously, as he could win or lose his past and future life.

Mr. Green entered a cubicle and touched the start button on the screen. A welcome message with his name appeared and a colorful image of his brain showed up. ‘‘It recognizes my biometrics’’ – he thought. Three available functions were displayed, ‘‘explore your brain,’’ ‘‘plan your surgery,’’ and ‘‘preserve your memories.’’

Mr. Green started with the first one. He was astonished with the ease he could navigate his brain and how the Cerefy Atlas was able to give him the name of any tiny structure along with description of its function. Mr. Green began to appreciate its potential. It was time to start doing the job.

He touched the second button. The nurse appeared and demonstrated how to distinguish on the images the normal from tumorous cells, and how to edit the resected region. It was quite easy with the Dextroscope stereoscopic display and a 3D reach-in, tactile user interface differentiating normal from pathological tissues. His hands reached into the brain space and worked as the tools reshaping the resected region. His future was really in his hands. He did not realize that he was the only person in the whole Brainsterium authorized to change the resection plan, as the system was monitoring the user’s

biometrics.

He started the inventory of his brain in the area of difference between the conservative and aggressive resection regions. Some skills were there that he might lose, such as climbing, driving, and playing the piano. He had given up his dream to climb K2 a long time ago. His personal driver was doing well so he would keep him. Playing the piano – no compromise.

He kept reshaping the region to be resected. The good-bye part of his brain was finally defined. Its knowledge and skills would be attempted to be recovered in a postoperative process. Now to memories and Mr. Green touched the last button. The button-called nurse appeared, put a BCC helmet on his head, and activated an array of transcranial magnetic stimulators.

‘‘I am lucky’’ – he thought – ‘‘she might have been a robot.’’

He projected his brain’s image, positioned the pointer within the region to be resected, and pressed the stimulation button. Nothing happened. He changed location and pressed the button again. Now he was watching the Titanic movie with his first love. He kept on pressing. It worked as a time machine moving him back to distant events and places. He could hardly believe that there were so many memories in such a small piece of tissue. Every memory he evoked was recorded. After the surgery, he would just play back any recorded piece to re-enter it into his brain.

The surgery plan was completed. He touched the submit button and was asked to confirm the plan and accept the legal statement. The session was terminated and he was invited for tea. The surgery would start in half an hour’s time. He loved this stuff. ‘‘I have got to subscribe to the Brainsterium Club, so I can come here every weekend for some brain surfing and unlocking’’ – he thought.

His new friend, the lion-robot ushered him to the Operating Rooms area. In this high-tech environment it looked so classic and trustworthy. Dr. Noki and the pretty nurse were already there.

Mr. Green laid down on the operating table, a BCC helmet was put on his head, and some monitoring probes attached to his body. ‘‘Are you ready?’’ – asked Dr. Noki and added – ‘‘Do not be afraid. Though the whole procedure is fully automatic, I will be controlling its every step.’’ Mr. Green pressed the start button initiating his own neurosurgery. The stereoscopic image of his brain was projected directly into his retinas and the resection plan prepared by him appeared. Initially, numerous sparkles surrounding the core tumor were visible. Later, he saw blood vessels feeding the core tumor being closed and the tumor separated from its surrounding tissues. Mr. Green felt an injection.

He noticed a wire going towards the tumor through the biggest blood vessel which remained still open. ‘‘This has to be a catheter’’ – he recalled. A magnetic system guided its tip automatically towards the tumor. The tip reached the tumor. A small balloon was inflated closing the vessel. The dissolved tumor tissues started disappearing fast. The space previously occupied by the core tumor kept on shrinking. Finally, the last blood vessel was closed. The surgery was over.

It was a long, eye-opening day for Mr. Green as a patient and investor. He had to stay overnight at the

Brainsterium under monitoring. Scanning was being performed automatically on continuous basis. Everything was normal as expected.

In the morning Mr. Green was discharged.

He went into Dr. Noki’s office and looked at him in a way that only a few multi-billionaires and CEOs deserved so far. ‘‘So far, so good’’ – Dr.Noki welcomed him. ‘‘We still have some work to do to recover the content of the resected part of your brain.

A disk was handed to Mr. Green. ‘‘My preserved memories’’ – he thought. Mr. Green was requested to keep on monitoring at home. He was given a wearable monitor capable of transmitting his scans from his home to the Brainsterium wirelessly. Finally he found some of his contribution.

Mr. Green’s driver brought him back home.

He realized that despite many urgent messages, he made one call only asking his secretary to donate anonymously to the Brainsterium’s R&D Center. He sat at his old grand piano and started playing his favorite pieces. He was quite happy with his technical performance and got an impression that he played even with a greater passion than before. Now he knew what he was going to invest in.

http://www.labmeeting.com/papers/author/tarnaris-a

Continuous intracranial pressure monitoring in pseudotumour cerebri: Single centre experience

Published in: Br J Neurosurg. 2010 Oct;24(5):584-8.

Continuous intracranial pressure monitoring in pseudotumour cerebri: Single centre experience.

Toma AK, Tarnaris A, Kitchen ND, Watkins LD.

Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. ahmedktoma@yahoo.com
Abstract
OBJECTIVE: Investigating pseudotumour cerebri (PTC) patients who do not fulfil the diagnostic criteria, or those presenting post-shunt insertion with recurrent symptoms and signs, with no clear evidence of shunt malfunction, present a diagnostic challenge. PTC patients who underwent continuous intracranial pressure (ICP) monitoring in our unit were reviewed retrospectively.
RESULTS: Twenty-six ICP monitoring procedures were done on 20 patients. Eleven patients had normal pressure, 2 overdrainage/low pressure, 11 underdrainage/high pressure and 2 variable pressures. On the basis of these results 12 patients were managed conservatively: 11 patients were referred to headache team and 1 patient had readjustment of an adjustable valve shunt setting; of those 3 patients had improved symptoms on their first post-operative clinic review. On the other hand, 14 patients had surgery: 5 had shunt revision and 9 had shunt insertion; of those 5 patients improved.
CONCLUSION: ICP monitoring using an intraparenchymal probe is a safe and effective diagnostic technique in investigating PTC when indicated. A multidisciplinary approach achieves best results in terms of successful management and follow-up