IMON FRASER/SCIENCE PHOTO LIBRARYTumor found in the cerebellum; hemangioblastoma compresses the area that controls coordination and balance IMON FRASER/SCIENCE PHOTO LIBRARY
The experience of having a rare disease that is difficult to diagnose, called normal pressure hydrocephalus, led Professor Sérgio Mascarenhas, coordinator of the Institute of Advanced Studies of São Carlos of the University of São Paulo (USP), to develop a piece of simple and minimally invasive equipment to monitor the internal pressure of the brain. It consists of a minute sensor placed immediately below the skin on the patient’s head and a special external monitor for receiving and analyzing information. The apparatus evaluates the volume of cephalorachidian liquid, or liquor, a substance that coats the central nervous system and protects it against impact, and also the concentration of blood and cerebral mass, as well as other risk factors that lead to an increase in pressure. Called the intracranial pressure monitor, the equipment that has already been patented, simplifies monitoring the clinical symptoms of people who have hydrocephalus, or are the victims of cranioencephalic trauma as a result of motorcycle or automobile accidents or falls.
Currently this examination is carried out by a sensor placed inside the brain, by means of an invasive surgical procedure and thus subject to infection. “As a researcher, I couldn’t reconcile myself to the fact that it was necessary to make a hole in someone’s head to measure pressure”, says Mascarenhas, a retired professor from the Physics Institute of USP in São Carlos, explaining the reason why, two years ago, he started more research at the age of 79, when he was still recovering from surgery that implanted a valve in his head to control the excess liquid produced because of a defect in the cerebral ventricle. The accumulation of liquid compresses the nervous tissue against the cranial box, causing symptoms such as dizziness, problems with coordinating movement and urinary incontinence. “The increase in intracranial pressure begins to compress the neurons and as a result this alters their functionality”, says Mascarenhas. As the disease mainly affects people over 60 the symptoms are commonly confused with those of Parkinson’s disease, making diagnosis difficult.
Measured deformation
The inspiration for development of the subcutaneous sensor, which measures intracranial pressure because of deformation produced by excess liquid in the skull, came from equipment used by engineers to monitor cracks in walls and the movement of beams, called a strain gauge. The first experiments were carried out on a workbench in the researcher’s home, with a skull he borrowed from the Federal University of São Carlos (UFSCar). “I got hold of the device they use for measuring the strain in beams in USP’s structure laboratory and placed it on the outside of the skull”, says the professor, who among his many other activities founded and directed Embrapa Agriculture and Livestock Instrumentation, a unit of the Brazilian Agriculture and Livestock Research Company [Embrapa] in São Carlos, and took part in setting up UFSCar and its materials engineering course (see interview with the researcher in Pesquisa Fapesp 137). As the skull is full of holes Mascarenhas had to fill it up to simulate intracranial pressure. He then used a colored rubber balloon left behind by his grandson, which was placed inside the skull and inflated. Mascarenhas wanted to simulate the pressure on the bone and the strain it causes. To complete the homemade experiment he dismantled a device for measuring blood pressure and used the pressure meter in millimeters of mercury to do the reading. The experiment consisted of comparing the external sensor with the one presently used inside the cranial box, and at the same time causing a variation in pressure to show that it was sensitive to induced changes. The results showed that he was on the right track.
After various experiments have been carried out with rats, rabbits and sheep, with comparisons being made between the invasive method and the subcutaneous sensor, the equipment will start being tested on 30 patients in the Clinicas Hospital of USP’s School of Medicine in Ribeirão Preto, in collaboration with the head of neurosurgery, Professor Benedicto Oscar Colli. “The patients with traumas who arrive at the hospital are going to receive both the traditional sensor and ours, so we can compare them”, says Mascarenhas. The device, which it was initially thought would be handling patients with hydrocephalus, will be used for any patient where there is a risk of an increase in intracranial pressure resulting from hemorrhage, edemas, tumors and infection.
EDUARDO CESARSubcutaneous sensor EDUARDO CESAR
Traffic accident victims with blows to the head and the cervical region will also benefit from monitoring, since the high cost of the current examination is an obstacle to using it on a large scale. “The traditional, disposable sensor, placed inside the brain, costs around R$ 5,000 for the imported one by Codman Johnson, and R$ 2,500 for the Brazilian one made by Ventura”, says the researcher. “The price of the monitor for the hospital is around R$ 30,000.” This is a big price difference compared to the apparatus developed by Mascarenhas. “The sensor is also disposable. It’ll cost around R$ 350 including tax, while the monitor will be around R$ 3,200”, is the comparison made.
Intracranial pressure is measured in millimeters of mercury, as is blood pressure. Under normal conditions intracranial pressure fluctuates to a certain extent depending on respiratory and cardiac cycles and measures from 5 to 15 millimeters of mercury (mmHg2). Between 20 and 30 characterizes intracranial hypertension caused by trauma or disease. Above this limit the patient may go into a coma. In the case of accidents involving cranial traumatism, for example, the pressure could be constantly monitored in the hospital with the new apparatus, thus avoiding many deaths. Currently this is not done because the traditional sensor is not available on the Single Health System (SUS) due to its high cost and the majority of accident victims have no way of paying for the procedure privately. It is this public that Mascarenhas wants to reach. “I refuse to be an academic who forgets that knowledge is to be used in the service of society”, he says.
Cranioencephalic traumatism is one of the most frequent causes of the increase in intracranial pressure in Brazil. Data from the SUS show that in 2007 alone, 98,945 cases of intracranial traumatism were notified, 12,800 cases of malignant neoplasias of the encephalus and 12,630 cases of hydrocephalus, totaling 124,375 occurrences with the potential to be monitored. “These numbers do not correspond to reality, because many patients die without being diagnosed”, says Mascarenhas. The tendency is that the number of traumatisms will increase even more, since every day more automobiles and motorcycles begin circulating in the country. “There are 430,000 automobile accidents a year, of which 35,000 result in death.” It was while the professor was thinking about this large number of patients that have no access to intracranial pressure monitoring that he decided to transform the subcutaneous sensor into a product, supported by FAPESP in the modality Innovative Research in Small Companies (Pipe). The company associated with the project is Sapra, from São Carlos, which operates in the area of health technology and was set up by the researcher in 1979. Today the person heading up the company is his daughter, Yvone Mascarenhas, a PhD in physics.
The tests to evaluate the biocompatibility of the sensor were carried out by PhD student, Gustavo Frigieri, a pharmacy and biochemistry graduate, whose tutor at the Physics Institute at USP is Professor Mascarenhas. On the 21st day after the sensor had been implanted in the head of a sheep, samples of tissue were collected and cytological and microbiological examinations carried out to assess the risks of allergy, inflammation or infection. “None of the three risks was observed”, says Frigieri. Mascarenhas emphasizes that this is an important aspect, because in the case of the traditional sensor the risk of infection means that it has to be removed after just a few days.
EDUARDO CESARSubcutaneous sensor tested initially on a skull EDUARDO CESAR
The subcutaneous sensor stayed in the sheep`s head for 21 days without any alteration in the normal state of the evaluated parameters. In the sheep the variation in intracranial pressure was induced by postural alterations, like raising and lowering the head, and by squeezing the jugular veins. Mascarenhas also assessed the pressure variations during an epilepsy attack in rats. The tests were done with a strain of audiogenic rats, in which epilepsy is induced by sound, that were bred by Professor Norberto Garcia-Cairasco, from the USP School of Medicine in Ribeirão Preto. “During a crisis, when the rat raises its head, it throws the liquor to the spinal column and the internal pressure in the brain is reduced”, says Mascarenhas. “When it lowers its head the liquor goes to the brain and the pressure increases.”
New assessments
While new experiments are being done to test the various applications of the sensor, Mascarenhas and his team, of which PhD student Wilson Seluque also forms part, are working on other, even more advanced methods for measuring intracranial pressure. One of them consists of a helmet, which on coming into contact with bone, functions like a sensor. In this case it will not even be necessary to shave the head to attach the sensor. “One of our study focuses is on knowing how intracranial pressure behaves during a migraine attack”, says the researcher, Or assessing the response of a brain tumor to chemotherapy. “If the tumor reduces in size intracranial pressure is going to go down”, he says, adding that monitoring the evolution of the disease can be done without the need for costly examinations. The idea is that in the future the intracranial pressure monitor will be transformed into a household item, like a thermometer or a blood pressure gauge, to make it possible to provide rapid help if intracranial pressure rises.
The project
Development of equipment for monitoring intracranial pressure in a minimally invasive way (nº 08/53436-2); Modality Innovative Research in Small Companies (Pipe); Coordinator Sérgio Mascarenhas – Sapra; Investment R$ 203,010.88 (FAPESP)
