Sunday, June 05, 2011

Recent advances in psychosurgery

Dr. Robert Hirschfeld wrote an Editorial in the Am. J. of Psychiatry concerning a paper published in the same Journal. We transcribe the following paragraphs from the Editorial. “In recent years several experimental neurosurgical procedures have been tried for severe intractable psychiatric disorders. Several of these procedures include targeted ablations such as anterior capsulotomy, anterior cingulotomy, and subcaudate tractotomy. An alternative to ablation procedures is intracranial electrical stimulation of targeted areas of the brain, or deep brain stimulation (DBS). This involves stereotactical implantation of intracranial electrodes that are connected to an implanted impulse generator in the chest wall. Advantages of DBS over lesioning include potential reversibility, revisability, and adjustability.
Research on the efficacy and safety of DBS for treatment-resistant depression has been limited to small open-label studies and case reports. The largest study to date involves 20 patients at several academic centers who received 6 months of DBS to the subcallosal cingulate gyrus (Brodmann’s area 25). To qualify for the study, patients had to be in an episode of major depression for at least 1 year and had to have failed to respond to at least four different treatments (including antidepres- sant, psychotherapy, and ECT). The initial 6-month response in these patients was 60%, and the remission rate was 30%. An article in this issue by Kennedy and colleagues (Kennedy SH, Giacobbe P, Rizvi SJ, Placenza FM, Nishikawa Y, Mayberg HS, Lozano AM: Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. Am J Psychiatry 2011; 168:502–510[Abstract/Free Full Text]) describes an extended follow-up (mean duration, 3.5 years) of these patients. The long-term outcome of these severely ill patients is encouraging. The average response rate at the last follow-up visit was 64%, and the remission rate was 35%. Psychosocial functioning and physical health had improved substantially over time, and there were no significant DBS-related adverse events."

Saturday, August 07, 2010

Psychosurgery is alive and well

There are many misconceptions circulating about leucotomy. It is widely believed that the intervention was completely abandoned. This is very far from reality. Indeed the development of drugs for the treatment of psychiatric disorders gave new horizons to the field. However, even the most successful of drugs had side effects ranging from barely tolerable to nearly lethal (Ivan Oransky, in Out of Mind, Schizophrenia, The Scientist, December 2007 supplement).

Different groups pursued psychosurgery with improved techniques. The following paper from the seventies describes good results with another approach:
Postgraduate Med. J. 1973, December, 49 (578) 865-882
Stereotactic limbic leucotomy—a follow-up study of thirty patients
Desmond Kelly and Nita Mitchell-Heggs
This prospective study reports the results of stereotactic limbic leucotomy at a mean of 17 months following surgery. Clinical improvement had occurred in twenty-four (80%) of the patients, fifteen (50%) of them being symptom free or much improved. Fourteen of sixteen patients suffering from obsessional neurosis were improved, as were five of seven with chronic anxiety and the degree of improvement at 17 months was superior to that at 6 weeks. Psychometric scores of anxiety, obsessions and neuroticism were all significantly reduced at 17 months. The mean depression scores were also significantly reduced and this result was superior to that reported in a previous study of ‘free-hand’ operations.
Adverse effects were not a problem following limbic leucotomy. Emotional blunting, disinhibition, post-operative epilepsy and excessive weight gain were not encountered, and intelligence was unaffected by the operation. Limbic leucotomy is a much more limited and precise procedure than older ‘free-hand’ operations which we have studied, but its therapeutic effects are comparable and in obsessional neurosis, superior.

Surgeons in Great Britain at the Wales University Hospital in Cardiff can target with an electrode introduced through a hole in the anterior side of the skull, areas of the brain the size of a pea. They perform the operation on carefully selected patients, with good results. They have conducted 56 operations during the last decade. Neurosurgeons at Ninewells Hospital in Dundee also have performed psychosurgery in 34 patients between 1990 and 2001. Moreover, Ballantine and his colleagues in Boston practice an operation called cingulotomy, a derivative of leucotomy, for depression and severe pain. It targets a tiny region of the cingulum and destroys it. The cingulum is a bundle of nerve fibers that runs from the back to the front of the brain, straddling the two cerebral hemispheres.

In November 2009 the New York Times reported that the Food and Drug Administration approved one of the psychosurgical techniques for some cases of obsessive-compulsive disorders. The paper also revealed that during the last decade more than 500 people have undergone brain surgery for problems like depression, phobias, anxiety, Tourette syndrome and obesity.
In the same article one can read the following comment: "The great promise of neuroscience at the end of the last century was that it would revolutionize the treatment of psychiatric problems. But the first real application of advanced brain science is not novel at all. It is a precise, sophisticated version of an old and controversial approach: psychosurgery, in which doctors operate directly on the brain. Such surgery offers both hope and risk".
The article mentions that the psychiatrist Dr. Benjamin Greenberg in charge of the psychosurgery program at Butler Hospital considers that in the future millions suffering from severe psychiatric conditions could benefit from brain surgery.

Egas Moniz made a prescient statement at the end of his last lecture when he retired from the Medical Faculty in 1944. He claimed that Neurology was at the dawn of a new era where surgery of the brain would be increasingly used to solve psychiatric problems. He cited the great Russian neurologist, Bechterew, who surprisingly had made the same claim in 1897.

Friday, August 10, 2007

The first patients submitted to leucotomy

An American blog that criticizes psychosurgery does biased descriptions concerning the first twenty leucotomyzed patients.

It is said for instance that patient eleven was diagnosed schizofrenic; actually Moniz hesitated between acute mania or schizofrenia.

Patient twelve is described as suffering from “cardiac neurosis”. As a matter of fact the diagnosis was anxiety neurosis based on a cardiopathy.

Patient thirteen is only reported in the psychosurgery blog as to have been excited for three months according to her son. The description by Moniz himself states that during those three months she had sleepless nights, left home at night, stole anything she could find, entered the neighbors’ homes, and imagined she was pregnant and should travel to Paris to deliver the baby. Moreover, thirty years before she had a period of melancholy that lasted five months, and 4 years before the melancholy lasted 2 years. During the latter period she remained all the time in bed without speaking to anyone.

It should also be added that the diagnosis of four of the patients was made by Moniz and his coworkers, the diagnosis of the other sixteen was made by a different group of psychiatrists in a different Hospital.

The followup of the first 20 cases operated by Almeida Lima and Egas Moniz revealed that 7 patients were cured, 7 other presented significant improvement, and in 6 changes could not be observed.

The American blog also criticizes the argument used to justify psychosurgery, i.e., the overload of Hospitals with patients. It mentions that most of those patients were not hospitalized or had been at the Hospital for a very short time. It should be remembered, though, that in Portugal at the time, because of the overload, patients remained with their families in spite of the burden it caused for their entourage.

The following gives an idea of how dramatic the situation was at the time in psychiatric Hospitals. Between 1940 and 1945, 40,000 patients died in France in psychiatric Hospitals, from hunger, cold, tuberculosis, neglect. A book entitled L’extermination douce by Max Lafon, describes this event.

The American blog does not mention any positive feature about psychosurgery. If it had no positive feature whatsoever it is difficult to understand why it was so widely used. It is known for instance that it “reliably decreased the symptoms of anxiety and depression” (DM Tucker et al. in Social and emotional self-regulation, Ann NY Acad Sci vol 769, p 213, 1995).

Sunday, June 25, 2006

Egas Moniz, leucotomy, and the Nobel Prize

A movement developed in the USA proposed the withdrawal of the Nobel Prize given to Egas Moniz for his surgical approach to some psychiatric diseases. It seems that this movement is supported by relatives from patients operated with a modification of the method of Egas Moniz. Indeed the operation modified by Walter Freeman in the USA was called lobotomy and was a much cruder procedure than the one initiated by Egas Moniz, which was called leucotomy. Freeman used a tool for the severing of neural fibers, which removed a much larger proportion of white matter. Moreover the surgical approach was different, in leucotomy the penetration was made from the side of the skull (parietal prefrontal leucotomy), in lobotomy the approach was through the orbit (frontal lobotomy). It is not Egas Moniz’ fault if his method was modified and used in patients for whom there was no justification for a surgical intervention. The modified procedure (lobotomy) was used by others indiscriminately often with dramatic consequences for the patients.
"It wasn't just the intrusiveness of those more radical procedures of lobotomy that caused the outcry but also the applications that certain proponents seemed to favor. The neurosurgeons Vernon H. Mark and William H. Sweet and the psychiatrist Frank R. Ervin, for example, wrote a letter to the Journal of the American Medical Association in 1967 that implied that psychosurgery might help quell the urban riots then sweeping the nation (USA); if, in each city, there were a handful of troublemakers with abnormalities of the amygdala, the troubles might have a medical explanation. These physicians seemed ready to diagnose as surgically treatable derangements of the brain, the violent outbursts that many viewed as a complex social problem". (Melvin Konner in Sciences, the publication of the NY Academy of Sciences)

It is also true that many patients benefited from leucotomy. As illustrated in an extensive British report a significant number of patients benefited from leucotomy. The Board of Control for England and Wales published in 1947 a survey collected from 97 public and 11 private psychiatric Hospitals concerning the outcome of 1000 leucotomies performed in those Hospitals. Among patients that left the Hospital 248 were considered cured, 105 improved, and 6 showed no improvement. Among patients still in the Hospital 323 showed improvement, 248 were considered unimproved, and in 10 the situation had become more severe. There were 33 relapses among those that left the Hospital and 12 among those still in the Hospital. There were 60 reported deaths. The report concluded that prefrontal leucotomy is in general an operation easy to perform for the patient although not always easy for the surgeon. Complications are not frequent. The number of deaths cannot be considered high if one takes into account the gravity of the mental diseases one is facing.
A significant improvement is observed in a large number of cases with serious symptoms and a dismal prognosis where all other methods of treatment have failed. Many patients submitted to prefrontal leucotomy leave the Hospital and others, although unable to return to social life, become quieter and easier to handle.
One cannot be certain yet whether the results are obtained with the loss of the finest, subtler mental qualities. Further studies are required to ascertain this point. Prefrontal leucotomy should be executed after a detailed evaluation of each individual case by experienced psychiatrists, concluded the british report.

More recently a paper published in the Archives of General Psychiatry by I.C. Bernstein et al. (1975, 32:1041-7) reported that in 43 private psychiatric patients who underwent prefrontal lobotomies between 1948 and 1970, 35 were virtually free of symptoms that prompted the operation, 6 had some improvement, and 2 were unimproved. The authors commented that “There is general agreement that high social class is a favorable prognostic feature……The supportive social environment seen so often in a private patients population is, we suggest, an important factor in our relatively high rate of success as compared with series from state hospitals”. This shows the multiple variables that could influence the outcome. Since the technique was not standardized, the outcome depended also very much on the ability of the surgeon. Another difficulty concerned the diagnosis of the psychiatric condition, which is still difficult and was even more difficult at the time. There is a growing body of opinion that schizophrenia is an umbrella term covering several diseases of differing etiology. Moreover, until a few years ago a patient labeled schizophrenic in the U.S. would likely have been called manic-depressive or neurotic in England and delusional psychotic in France (Lynn Payer, Medicine and Culture, Viking Penguin).

When Egas Moniz died, Professor Sir Geoffrey Jefferson expressed in The Lancet from December 31, 1955 (page 1397) his warm appreciation for the work of the Portuguese scientist. He wrote: “His life was an unusually productive one, his name will live for his two great contributions to medicine. No one who was privileged to watch the development of Egas Moniz’s discoveries could help but admire the ways in which they were developed. Humanity has reason to pay its last respects and express its gratitude to another great Portuguese explorer".

There is an excellent site dedicated to Prof. Egas Moniz, it describes different aspects of his life, not only his scientific work. One can also visit the interior of his country home and birth place, which became a museum. All sort of references related to his daily life can be found at the site. The address is
The site is still in the making and new data will be added.

Saturday, June 17, 2006

Surgical interventions to the frontal lobes before Egas Moniz started leucotomy

It was known that it is possible to remove one of the frontal lobes, left or right, without severe consequences to psychic integrity. At most the perturbations are transitory, the remaining lobe performs the function of the excised lobe.

Penfield and Evans had performed the excision of the left frontal lobe in a man 22 years old with epileptic seizures. The patient became mentally confused and also space and time disoriented during the first week after the operation. Those symptoms regressed progressively and six months later the patient had return to normal behaviour.

Wilder Penfield also removed the two frontal lobes on a patient with a large brain tumor.

Richard Brickner removed large portions of the two frontal lobes for the excision of a meningioma. He noticed pronounced changes of the mental activity. The patient forgot previous experiences and became like a child who had to learn again how to behave socially. The patient recovered progressively, however, with the preservation of a large part of his psychic functions, keeping essentially his personality although more childish in some regards.

An estonian surgeon, Ludwig Puusepp, reported in 1937 that years earlier he had severed the neural links between the frontal and the parietal lobes in three patients with manic depression. The surgery, however, had done no good . Later he performed leucotomy-like operations on fourteen patients with generally good results (Jack el-Hai in “The Lobotomist”, John Wiley & Sons, Inc.).

Tuesday, March 21, 2006

Distortions about Egas Moniz' scientific life

There are several fantasies circulating regarding the career and personality of Egas Moniz. Elliot Valenstein in his book “Great and Desperate Cures”, says that Moniz’s main motive was to achieve in his declining years the recognition that a rather mediocre career had otherwise failed to bring, by gambling on the success of an operation so drastic that nobody else would dare to perform it. As a matter of fact, Egas Moniz was already world famous for his discovery of cerebral angiography, when he attempted psychosurgery. Before receiving the Nobel Prize, he was awarded the Oslo Prize for angiography, a method that was extended to other organs, which is still in use today, and which saved thousands of lives.

Valenstein also claimed that Moniz was inspired to undertake the operation by witnessing two monkeys, which had been made placid by lesions to their frontal lobes. Besides an extensive literature about the frontal lobes Moniz mentions in his memoirs not only the experiments of Fulton and Jacobson in chimpanzees but also those of Bechterew and Luzaro in dogs where the frontal lobes were removed resulting in a modification of the behavior of the animals. The truth is that Moniz was also inspired by the description of brain injuries suffered by soldiers during the First World War, and by the changes occurring in patients with tumors and other lesions of the frontal lobes; there was an abundant literature concerning the modifications in behavior subsequent to lesions of the frontal lobes either due to tumors or to mutilations suffered in combat. He had published in 1917 a book entitled "A Neurologia na Guerra" (Neurology during War) describing brain injuries and its consequences from data collected during the First World War. So as described below the reasoning was much more elaborate.

Egas Moniz first scientific contribution was the description of sexual behavior of human beings and its perversions collected from interviews. This work was published in a book entitled Sexual Life and constitutes several decades before Kinsey’s report in the USA, the first such description.

His second main contribution achieved in 1925, consisted in the visualization of the blood circulation of the brain. In the words of G.A. Donnan (The Lancet 1993, 341:796) “The technique of intra-arterial cerebral angiography has subsequently proved to be one of the commonest and most durable investigations in neurology”.

The descriptions, by Moniz himself, of the experiments that led finally to the application of angiography in medical practice, gives to the reader an excellent picture of what research is like. It took five years from the first experiment in dogs and human cadavers to the use of the technique in routine diagnosis. Moniz first used a 25% sodium iodine solution to obtain the X-ray contrast. Later in 1931 two of his followers used a thorium solution (thorotraste). This is described in his autobiography.

Angiography is important not only for the diagnosis and localization of brain tumors rendering them operable; it also allowed the elucidation of the circulatory network making possible the removal of aneurisms. For the first time it became possible to follow in the living organism a dynamic event, this was a revolution. The technique was rapidly extended to other areas and organs of the body, with vast implications for basic physiology, pathology, and for medical practice. The importance of a scientific achievement is measured in terms of the contribution it makes beyond the field where it was first performed; Angiography ranks among this type of achievements. Egas Moniz received the Oslo Prize for this contribution.

Angiography led to another important contribution, it concerned the study of internal carotid occlusion. We suggest the reading of the following paper: "The Neglected Research of Egas Moniz of Internal Carotid Artery (ICA) Occlusion". George W. Lowis and Alireza Minagar, Journal of the History of the Neurosciences: Basic and Clinical Perspectives, Volume 12, Issue 3, 2003, pages 286-291.
"Egas Moniz is generally remembered for having discovered cerebral angiography in 1927, and having introduced lobotomy as a form of treatment for mental illness in 1935. Less well known is his pioneering research on occlusive cerebrovascular disease, namely internal carotid artery (ICA) occlusion, as documented by cerebral angiography. It is our contention that the medical community has, until recently, largely overlooked this research. His neglected observations on ICA occlusion and the important diagnostic role played by angiography are reviewed. We propose to show how our paper differs from previous publications regarding Moniz's ICA occlusion contributions. Whereas most previous reviews have focused on either the role played by cerebral angiography in the diagnosis of ICA occlusion, or on the importance of Moniz's internal carotid occlusion observations, our review attempts to integrate both topics. We will tie Moniz's ICA occlusion research to his documented use of angiography."

Friday, March 17, 2006

Rationale for leucotomy

I heard some naïve statements on how Egas Moniz conceptualized leucotomy. One story goes that he entered a room where there was a skull on a table; he pointed to one side of the skull and said: here is where we have to pierce.

The idea of treating obsessive psychoses with surgery did not occur suddenly, it was rather the product of long thoughts and search in the literature that started in 1933 and went on during the following two years. Reading about the changes in personality resulting from accidental lesions to the frontal lobes, he concluded that this region was the center of emotions, that it should control the majority of the stimulations originated externally and internally. The data suggested that the frontal lobes are a kind of central hub reached directly or indirectly by most fiber connections. Moreover, because of its larger volume there was a tendency at the time to attribute to the left frontal lobe a particular role in psychic activity.

Based on the histological structure described by Cajal and on the experiments of Pavlov, he thought that obsessive psychoses would dominate all the other psychic activities through reiterated influxes using the same connections. Pavlov obtained in the dog a new pathway resulting from an induced repeated stimulus. Moniz thought that established new circuits could be abolished if the connections to other regions would be severed. He discussed his thoughts with many colleagues and looked for advice whether he should go ahead.

John Fulton several years after the first leucotomies also suggested that “interrupting the vicious circles which form the basis of abnormal states” could successfully treat psychiatric disorders (Jack el-Hai in “The Lobotomist”, John Wiley & Sons, Inc.)

Studies of the brains of patients with schizophrenia indeed suggest altered function in the prefrontal cortex, the brain's organizational center for cognitive function, personality expression, and behavioral control. It is interesting that Torrey’s Washington team found that schizophrenics failed to activate a region within the frontal lobe, technically known as the dorsolateral prefrontal cortex. Torrey said that this seems to imply that schizophrenia is a breakdown of particular areas in the brain in the connections between them, most likely on the brain’s left side. (Tony Dajer in “Divided Selves”, Discover 13(9):38-44; 69, Sep 92)

Brian Kirkpatrick from the University of Maryland School of Medicine in Baltimore has argued that in schizophrenia a flawed brain circuit has possibly been identified, based in part on evidence of impaired frontal and parietal function revealed by PET scans of the thalamic, frontal and parietal areas. (T.M. Powledge in Academy Update, NY Academy of Sciences, June/July 1996)

Moreover, a team from the Albert Einstein College of Medicine in New York found brain abnormalities in schizophrenic children suggesting changes that disrupt the transmission of signals that regulate behavior. The researchers used a sophisticated scanning technique called diffusion tensor imaging. They found abnormalities in white matter of the frontal lobe, which controls emotions and many thinking processes.

A spanish group from the Centros de Investigación Biomédica en Salud Mental headed by Edith Pomarol-Clotet identified structural and functional alterations in the frontal cortex of 32 schizophrenic patients. The work was published in 2010 in the Journal Molecular Psychiatry.

The prefrontal cortex is now considered to be the seat of the most complex and uniquely human activities (G. Miller, Science vol 311, 2006, p. 1851).