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Bloodless Surgery

Gamma rays help in the treatment of obsessive-compulsive disorders

EDUARDO CESARCanteras checks on the examinations before surgery: reduced collateral effectsEDUARDO CESAR

The surgery lasted close to twelve hours. The preparations for surgery began early in the morning when the final magnetic resonance imaging exams determined the exact area of the brain to be hit. With the map in their hands, the doctors led the patient to the operating room: he was a patient with a serious psychiatric problem, obsessive-compulsive disorder, more commonly known as OCD, which could not be controlled by any other manner.

The patient lay down on the bed in the radioactive cobalt chamber, much like the magnetic resonance equipment, and was sedated. He was already asleep when they placed a metal dome that looked like a helmet, with 201-millimeter holes. It was through these holes that the gamma rays coming from the apparatus passed in the direction of a single point in the brain. The radiation, in variable intensity, eliminated a specific group of neurons involved with the problem. The patient went home the next day without having suffered a single cut.

Since December when five surgeries of this type were performed for the first time in Brazil, on people whose names are not being disclosed, a mixture of feelings caution, anxiety, and satisfaction have accompanied Eurípedes Constantino Miguel’s team at the Psychiatric Institute of the School of Medicine of the University of Sao Paulo (USP). Although the five operations were watched over by specialists from Brown University, in the United States, where at least fifty people have already undergone the same process, doubt persists: Will it work? Up until now, according to the first examinations, all of the operated patients are doing fine. But definite results will only be known at the end of the year, since the effects of the radiation only become more marked starting from the third month after the operation.

If all goes well in these experimental studies, the USP group could announce an alternative in the treatment of patients who show the most severe form of obsessive-compulsive disorder (OCD), which affects close to 2% of the world ‘s population in Brazil, there are a little over 3 million people with this problem. The operated patients belong to a group of around 10% of the diagnosed cases that for some unknown reason have gone through at least five years of treatment without any positive result.

The daily OCD carriers is endless suffering. Persecuted by irrepressible thoughts, they are capable of walking round the block for hours, with the fear of having knocked someone over without having noticed. Sometimes, they feel the need to wash their hands hundreds of times until they bleed, because they believe that they are always dirty. They have a mania for putting things in order and cannot see objects out of line or out of place. They collect piles of worthless paper. At the peak of despair and of losing control, they think about suicide. “The obsessions, which are the strange thoughts and the absurd images that constantly come to their minds, cause intense torment and lead them to repetitive practices”, says Antonio Carlos Lopes, one of the USP team ‘s doctors.

In his opinion, the carriers of OCD are conscious of their exaggerations, but cannot manage to free themselves from them. For this reason, they normally stop studying, stop having a social life and live fighting with their families, who don’t always understand the need for their rituals.

With the other possibilities of treatment worn out, the still experimental alternative for the most resistant cases is a type of neurosurgery known as anterior stereotactic capsulotomy by hamma-knife: small doses of gamma radiation in themselves incapable of damaging the cell of the nervous system, converge towards a point, which, according to the examinations, has had an abnormal working pattern. Then, as the rays cross over, they become lethal.

Put into practice for cases of OCD almost ten years ago at Brown University, this type of radio-surgery had been used to combat tumors, with almost 200,000 cases already treated, and as an alternative in the treatment of epilepsy and Parkinson ‘s disease, resistant to conventional therapies. Confident in the results, the USP researchers have begun to think about the next stage: a large scale study, with at least 48 patients with OCD divided into two groups one would be submitted to neurosurgery and the other, to a false operation with all of the procedures, but without the release of the gamma rays. Definite conclusions about the efficiency of this approach would only become known after five years.

It is believed that obsessive-compulsive disorder results from the malfunctioning of the circuits that connect structures located in the proximity of the base of the brain (the nucleus of the base) to the cortex, the most external layer. Another possible cause is communication errors between the neurons made by way of serotonin, one of the neurotransmitters existing in the nervous system.

When the inefficiency of the two conventional approaches is confirmed based on anti-depressive medicines that do augment the quantity of serotonin in the nerve connections, or of behavioral therapy, another surgical technique frequently adopted is the so called anterior cingulotomy: through an opening in the cranium an electrode in the shape of a hair is placed, which, by way of radio waves, burns the neurons of a specific stretch of the brain, a part of the circuit involved in OCD, like the cingulate gyrus.

On the other hand, the Gamma-knife technique acts on deep areas of the brain. The gamma rays eliminate the cells of a structure called the internal capsule, formed by nerve fibers that go across the nucleus of the base and link to the thalamus (responsible for interpreting the sensations of touch, pain and temperature) to the frontal cortex. The intention is the same to destroy the neurons that previously functioned in excess, with the advantage that the cranium does not need to be opened and side effects are less.

“In the operated patients we did not observe hemorrhages, convulsion, nor infections, which that can occur in other neurosurgeries”, explains Miguel Canteras, the project ‘s neurosurgeon. The most dreaded effect is a swelling of the brain that has to be controlled with anti-inflammatory medicines.

Canteras made an issue of separating any association of these two procedures with lobotomy, the first surgical technique used for the treatment of mental problems. Created during the 30’s, it was widely used on individuals with schizophrenia or even with anxiety or exacerbated aggressiveness. Lobotomy consists in extracting extensive areas that link the frontal lobos to the rest of the nerve system, with grave impacts: it was almost impossible to avoid alterations in personality and cognitive disturbances. “There was no notion of the consequence of the lesions provoked by a lobotomy”, he said. “Today we are in another phase and the neurosurgeries are carried out in accordance with clinical and ethical norms.”

Origins
Besides searching for treatment options, the USP team has been studying the very origin of OCD. One of the main pieces of work from the group confirmed the relationship, up until that point only suspected, between the symptoms of obsessive-compulsive disorder and rheumatic fever, an autoimmune disorder caused by antibodies produced by the organism itself to combat bacteria.

Rheumatic fever causes pain in the throat, reddening of the skin and, in an advanced phase it can reach the central nervous system and this is when it gets associated to another neurological problem, Sydenham’s chorea, with involuntary movements of the arms and legs, associated with the malfunctioning of the nucleus of the base. The researchers evaluated 22 children who demonstrated rheumatic fever and chorea and a further 20 only with rheumatic fever. Afterwards they compared the data with that from 20 members of the control group, children without autoimmune disorders.

In the first group, almost half the children suffered from OCD or showed obsessive-compulsive symptoms, but as yet not intensive enough to characterize the typical picture of OCD. In the group with rheumatic fever, the level of OCD carriers or those with traces of obsessive-compulsive disorder was also high (35%), whilst there were no cases of this psychiatric illness in the children without auto-immune illnesses.

“Rheumatic fever, associated or not with Sydenham ‘s chorea, is a risk factor for OCD”, says Marcos Mercadante, another researcher with the group. His colleague Ana Hounie confirmed that in families with children who have rheumatic fever (with or without chorea), the probability of finding a first line relative also with obsessions and compulsions is three times greater than in the control group, formed by families of children without rheumatic fever. “The work suggests that the rheumatic fever could be genetically linked to OCD”, says Ana, whose results should come out shortly in the Journal of Clinical Psychiatry.

In another line of research, Euripedes ‘s team fist suspected and then confirmed that OCD is not a single disease, but a group of similar infirmities, which differ in their intensity and in the type of symptoms presented. The USP researchers followed up 42 patients with OCD, dividing them up into two groups according to the date of the start of the symptoms.

In the patients called precocious (the illness having started by ten years of age), the intensity and the gravity of the problems were much worse than those in the group called late starters, beginning at seventeen. “In the younger group manias such as collections and repetitions were much more intense, ticks were constant and the response to treatment with medicines less”, explains Maria Conceição Rosário Campos. The results reinforce the hypothesis that there is not just a single type of OCD, but specific subgroups, with characteristics and diverse manifestations.

The Project
Pathogenesis and the Treatment of Obsessive-Compulsive Disorder (nº 99/12205-7); Modality Thematic Project; Coordinator Euripedes Constantino Miguel Filho University of Sao Paulo; Investment R$ 677,449.05

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