Temporal Lobe Epilepsy

 

 

There are over 40 types of epilepsies which fall into two main categories: A). partial-onset (focal or localization-related) and B) generalized-onset. Partial-onset epilepsies account for about 60% of all adult epilepsy cases, and temporal lobe epilepsy (TLE) is the most common single form causing refractory epilepsy.

 

TLEs are a group of medical disorders in which humans and animals experience recurrent epileptic 1) ___ arising from one or both temporal lobes of the brain. Two main types are internationally recognized according to the International League Against Epilepsy. Mesial temporal lobe epilepsy (MTLE) arises in the hippocampus, parahippocampal gyrus and amygdala which are located in the inner aspect of the temporal lobe, while lateral temporal lobe epilepsy (LTLE) arises in the neocortex on the outer surface of the temporal lobe of the brain. Because of strong interconnections, seizures beginning in either the medial or lateral temporal areas often spread to involve both areas and also to neighboring areas on the same side of the 2) ___ as well as the temporal lobe on the opposite side of the brain. The causes or etiology of different temporal lobe epilepsies vary and are discussed below.

 

Syndrome of Temporal Lobe Epilepsy: The classical syndrome of TLE or 3) ___ ___ ___ may begin when there is a very early insult to the left or right hippocampus that causes neuron death. Infants may develop lung or skin infections resulting in a fever. Babies have an immature thermoregulation system, and the fever causes the baby’s core body temperature to increase more drastically than in adults. In some children, elevated body 4) ___ can cause febrile seizures. Febrile seizures are relatively normal as they occur in 2-5% of children under age 5 years. They typically last only a few minutes or even a matter of seconds, but are neither severe motor convulsions nor followed by weakness on one side of the body. In a small number of babies, these convulsions can last for over an hour and involve repeated convulsive episodes. These are known as complex febrile seizures and may be causatively associated with TLE. It remains controversial whether complex febrile seizures actually cause TLE, or whether they are simply the earliest manifestation of the TLE condition.

 

Causes: A link between febrile seizures (seizures coinciding with episodes of 5) ___ in young children) and subsequent temporal lobe epilepsy has been suggested, but the exact role remains unclear. Some studies have shown abnormalities of the hippocampus on magnetic resonance imaging (MRI) in status epilepticus, which supports the theory that prolonged seizures damage the brain. Interestingly, some cases of MTLE present without the typical changes of mesial temporal sclerosis or other abnormalities on MRI scans. This has been termed paradoxical mesial temporal lobe epilepsy. The epilepsy in these patients tends to occur at a later age, which might suggest that an early event leads to hippocampal damage causing MTLE. Although this theory needs confirmation, some studies have pointed to human herpes virus 6 (HHV-6) as a possible link between febrile convulsions and later MTLE. Some studies suggest that HHV-6 infection happens prior to the occurrence of febrile seizures. However, only a minority of primary HHV-6 infections may be associated with febrile seizures. Secondly, other studies found HHV-6 DNA in brain tissue removed during surgery for MTLE. Rarely, MTLE can be hereditary or related to brain 6) ___, spinal meningitis, encephalitis, head injury or blood vessel malformations. MTLE can occur in association with other brain malformations. Most often, a cause cannot be determined with certainty.

 

LTLE: LTLE can be hereditary, as in Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTLE) with auditory or visual features, but it can also be associated with tumors, meningitis, encephalitis, trauma, vascular malformations or congenital brain malformations. Again, in many affected persons it is common that no cause can be identified. Dispersion of granule cell layer in the hippocampal dentate gyrus is occasionally seen in temporal lobe epilepsy and has been linked to the down-regulation of reelin, a protein that normally keeps the layer compact by containing the neuronal migration. It is unknown whether changes in reelin expression play a role in 7) ___.

 

Symptoms: The symptoms felt by the person, and the signs observable by others, during seizures which begin in the temporal 8) ___ depend upon the specific regions of the temporal lobe and neighboring brain areas affected by the seizure. The International Classification of Epileptic Seizures published by the International League Against Epilepsy (ILAE) recognizes three types of seizures which persons with TLE may experience.

 

1. Simple Partial Seizures (SPS) involve small areas of the temporal lobe such as the amygdala or the hippocampus. The term “simple” means that consciousness is not altered. In temporal lobe epilepsy SPS usually only cause sensations. These sensations may be amnestic such as deja vu (a feeling of familiarity), jamais vu (a feeling of unfamiliarity), a specific single or set of memories, or amnesia. The 9) ___ may be auditory such as a sound or tune, gustatory such as a taste, or olfactory such as a smell that is not physically present. Sensations can also be visual, involve feelings on the skin or in the internal organs. The latter feelings may seem to move over the body. Psychic sensations can occur such as an out-of-body feeling. Dysphoric or euphoric feelings, fear, anger, and other sensations can also occur during SPS. Often, it is hard for persons with SPS of TLE to describe the feeling. SPS are often called “auras” by lay persons who mistake them for a warning sign of a subsequent seizure. In fact, they are indeed seizures. Persons experiencing only SPS may not recognize what they are or seek medical advice about them. SPS may or may not progress to the seizure types listed below.

 

2. Complex Partial Seizures (CPS) by definition are seizures which impair 10) ___ to some extent. This is to say that they alter the person’s ability to interact with his or her environment. They usually begin with an SPS, but then the seizure spreads to a larger portion of the temporal lobe resulting in impaired consciousness. Signs may include motionless staring, automatic movements of the hands or mouth, altered ability to respond to others, unusual speech, or unusual behaviors.

 

3. Secondarily Generalized Tonic-Clonic Seizures (SGTCS): begin in the temporal lobe but then spread to the whole brain are known as. These begin with an SPS or CPS phase initially, but then the arms, trunk and legs stiffen (tonic) in either a flexed or extended position and then clonic jerking of the limbs often occurs. GTCS are often known in the vernacular as convulsions or “grand mal” (originally a French term) seizures. Following each of these seizures, there is some period of recovery in which neurological function is altered. This is called the postictal state. The degree and length of the impairment directly correlates with the severity of the 3 seizure types listed above. SPS often last less than 60 seconds, CPS often last less than 2 minutes, and SGTCS usually last less than 3 minutes. The postictal state in the case of CPS and GTCS often lasts much longer than the seizure ictus itself. Because a major function of the temporal lobe is short-term memory, CPS and GTCS cause amnesia for the seizure. As a result, many persons with temporal lobe CPS and GTCS will not 11) ___ having had a seizure.

 

Driving: Local and national laws exist regarding the operation of vehicles, aircraft and vessels by patients with epilepsy. Most licensing departments do not allow driving of vehicles by persons with CPS or GTCS until they have been seizure-free for a specified period of time. The laws are complex and varied; affected persons must check with the appropriate licensing authority. In a few locations, health care providers are legally-required to report patients with epilepsy (and other medical conditions which cause episodes of altered consciousness) to their local department of motor vehicles.

 

Temporal Lobe Epilepsy, Neurotheology and Paranormal Experience: The first researcher to note and catalog the abnormal experiences associated with TLE was neurologist Norman Geschwind, who noted a constellation of symptoms, including hypergraphia, hyperreligiosity, fainting spells, and pedantism, often collectively ascribed to a condition known as Geschwind syndrome. Vilayanur S. Ramachandran explored the neural basis of the hyperreligiosity seen in TLE using galvanic skin response (which correlates with emotional arousal) to determine whether the hyperreligiosity seen in TLE was due to an overall heightened emotional state or was specific to religious stimuli (V. Ramachandran and Sandra Blakeslee, 1998). By presenting subjects with neutral, sexually arousing and religious words while measuring GSR, Ramachandran was able to show that patients with TLE showed enhanced emotional responses to the religious words, diminished responses to the sexually charged words, and normal responses to the neutral words. These results suggest that the medial 12) ___ lobe is specifically involved in generating some of the emotional reactions associated with religious words, images and symbols.

 

Cognitive neuroscience researcher Michael Persinger asserts that stimulating the temporal lobe electromagnetically can cause TLE and trigger hallucinations of apparent paranormal phenomena such as ghosts and UFOs. Persinger has even created a “God helmet” which purportedly can evoke altered states of consciousness through 13) ___ of the parietal and temporal lobes. Neurotheologians speculate that individuals with temporal lobe epilepsy, having a natural tendency to experience states of consciousness such as euphoria or samadhi, have functioned in human history as religious figures or shamans.

 

ANSWERS: 1) seizures; 2) brain; 3) temporal lobe epilepsy; 4) temperature; 5) fever; 6) tumors; 7) epilepsy; 8) lobe; 9) sensations; 10) consciousness; 11) remember; 12) temporal; 13) stimulation

Vincent Van Gogh (1853-1890)

 

Vincent c.1871–1872 aged 18. This photograph was taken at the time when he was working at the branch of Goupil & Cie’s gallery at The Hague

 

 

Vincent Van Gogh’s Mental and Physical Health: Because countless, physicians and psychiatrists have tried to define Van Gogh’s medical conditions over the years, there is much literature to draw from. A certain amount of controversy still exists, i.e. whether or not Van Gogh committed suicide. In addition to the writings of physicians, another valuable source of information are the letters of Vincent Van Gogh and his brother Theo. The following are some of the more probable mental and physical diagnoses.

 

Temporal Lobe Epilepsy: Van Gogh suffered from seizures which doctors, including Dr. Felix Rey and Dr. Peyron, believed to be caused by temporal lobe epilepsy. Van Gogh was born with a brain lesion that many doctors believe was aggravated by his prolonged use of absinthe causing his epileptic condition. Dr. Gachet, another of Van Gogh’s physicians, was thought to have treated his epilepsy with digitalis. This prescription drug can cause one to see in yellow or see yellow spots which may have been one of the reasons why Van Gogh loved this color.

 

Bipolar disorder: Due to Van Gogh’s extreme enthusiasm and dedication to first religion and then art coupled with the feverish pace of his art production many believe that mania was a prominent condition in Van Gogh’s life. However, these episodes were always followed by exhaustion and depression and ultimately suicide. Therefore, a diagnosis of bipolar disorder or manic depression makes sense with the accounts of these episodes in Van Gogh’s life.

 

Thujone poisoning: In order to counter act his attacks of epilepsy, anxiety, and depression, Van Gogh drank absinthe, a toxic alcoholic drink popular with many artists at the time. Thujone is the toxin in absinthe. Unfortunately, thujone worked against Van Gogh aggravating his epilepsy and manic depression. High doses of thujone can also cause one to see objects in yellow. Various physicians have differing opinions on whether or not this is what caused Van Gogh’s affinity with yellow.

 

Lead poisoning: Because Van Gogh used lead based paints there are some who believe he suffered from lead poisoning from nibbling at paint chips. It was also noted by Dr. Peyron that during his attacks Van Gogh tried to poison himself by swallowing paint or drinking kerosene. One of the symptoms of lead poisoning is swelling of the retinas which can cause one to see light in circles like halos around objects. This can be seen in paintings like The Starry Night.

 

Hypergraphia: Hypergraphia is a condition causing one to need to write continuously; this disorder is commonly linked to mania and epilepsy. Some believe that the massive collection of over 800 letters Van Gogh wrote during his lifetime could be attributed to this condition.

 

Sunstroke: Because Van Gogh strived for realism in his paintings he was often painting outdoors especially during his times in the South of France. Some of his episodes of hostility and the nausea and “bad stomach” he refers to in his letters may have been the effects of sunstroke.

 

In 2011, authors Steven Naifeh and Gregory White Smith published a biography, Van Gogh: The Life, in which they challenged the conventional account of the artist’s death. In the book, Naifeh and Smith developed an alternative scenario in which Van Gogh did not commit suicide, but rather was a possible victim of manslaughter or foul play.Naifeh and Smith point out that the bullet entered Van Gogh’s abdomen at an oblique angle, not straight as might be expected from a suicide. They claim that van Gogh knew the boys who may have shot him, one of whom was in the habit of wearing a cowboy suit, and had gone drinking with them. The authors contend that art historian John Rewald visited Auvers in the 1930s, and recorded that version of events was widely believed. The authors postulate that after he was fatally wounded, Van Gogh welcomed death and believed the boys had done him a favor, hence his widely-quoted death-bed remark: “Do not accuse anyone, it is I who wanted to kill myself.”

 

Vincent van Gogh: Ward in the Hospital in Arles (1889)

 

 

The death of Vincent van Gogh, the Dutch post-Impressionist painter, occurred in the early morning of 29 July 1890, in his room at the Auberge Ravoux in the village of Auvers-sur-Oise in northern France. He suffered a gunshot wound two days earlier not far from the inn.

 

Deteriorating mental health: In 1889, Vincent van Gogh experienced a deterioration in his mental health. As a result of incidents in Arles leading to a public petition, he was committed to hospital. At the suggestion the Reverend Salles, an acquaintance of the artist, Van Gogh’s brother Theo persuaded him to spend some time in an asylum in nearby Saint-Rémy in the hope that his health would improve.He entered the asylum on a voluntary basis in early May 1889. His mental condition did not improve and considerably worsened the following December and in the early months of 1890

 

Changing mood at Auvers from May 1890: Shortly before leaving Saint-Rémy, Van Gogh told how he was suffering from his stay in the hospital: “The surroundings here are beginning to weigh me down more than I can say   I need some air, I feel overwhelmed by boredom and grief.” On arriving at Auvers, Van Gogh’s health was still not very good. Writing on 21 May to Theo he comments: “I can do nothing about my illness. I am suffering a little just now Rémy – the thing is that after that long seclusion the days seem like weeks to me.” But by 25 May, the artist was able to report to his parents that his health had improved and that the symptoms of his disease had disappeared.His letters to his sister Wilhelmina on 5 June and to Theo and his wife Jo on about 10 June indicate a continued improvement, his nightmares almost having disappeared.

 

On about 12 June, he wrote to his friends Mr. and Mrs. Ginoux in Arles, telling them how his health had suffered at Saint-Rémy but had since improved: “But latterly I had contracted the other patients’ disease to such an extent that I could not be cured of my own. The other patients’ society had a bad influence on me, and in the end I was absolutely unable to understand it. Then I felt I had better try a change, and for that matter, the pleasure of seeing my brother, his family and my painter friends again has done me a lot of good, and I am feeling completely calm and normal.”

 

Furthermore, an unsent letter to Paul Gauguin which Van Gogh wrote around 17 June is quite positive about his plans for the future. After describing his recent colorful wheat studies, he explains: “I would like to paint some portraits against a very vivid yet tranquil background. There are the greens of a different quality, but of the same value, so as to form a whole of green tones, which by its vibration will make you think of the gentle rustle of the ears swaying in the breeze: it is not at all easy as a color scheme.” On 2 July, writing to his brother, Van Gogh comments: “I myself am also trying to do as well as I can, but I will not conceal from you that I hardly dare count on always being in good health. And if my disease returns, you would forgive me. I still love art and life very much.”

 

The first sign of new problems was revealed in a letter Van Gogh wrote to Theo on 10 July. He first states, “I am very well, I am working hard, have painted four studies and two drawings,” but then goes on to say, “I think that we must not count on Dr Gachet at all. First of all, he is sicker than I am, I think, or shall we say just as much, so that’s that. I don’t know what to say. Certainly my last attack, which was terrible, was in a large measure due to the influence of the other patients.” Later in the letter he adds, “For myself, I can only say at the moment that I think we all need rest – I feel exhausted.” In an even more despairing tone he adds: “And the prospect grows darker, I see no happy future at all.” In another letter to Theo on about 10 July1890, Van Gogh explains: “I try to be fairly good-humored in general, but my life too is threatened at its very root, and my step is unsteady too.” He then comments on his current work: “I have painted three more large canvases. They are vast stretches of corn under troubled skies, and I did not have to go out of my way very much in order to try to express sadness and extreme loneliness.” But he adds, “I’m fairly sure that these canvases will tell you what I cannot say in words, that is, how healthy and invigorating I find the countryside.”

 

The Life of van Gogh

 

Origins: Vincent van Gogh’s ancestry includes Dutch preachers, art dealers, and artisans. Both his father and paternal grandfather were preachers; his paternal great-grandfather was a gold wiredrawer who also was a catechism teacher. No incidences of mental illness are recorded among van Gogh’s ancestors. His mother married at the age of 31, had a stillborn first son, and 1 year later gave birth to Vincent. Vincent was a moody child, self-willed, and often annoying. At the age of 12, he was sent to a boarding school for the next 4 years. A photograph of Vincent as an adolescent and later self-portraits suggest a significant craniofacial asymmetry. Gastaut submitted that this physical feature and early temperamental changes suggest that Vincent had suffered an early brain injury, probably at birth. His intense emotionality, which was evident early and became frequently unbearable in his adult life, is set forth in his own statement: “I am a man of passion, capable and prone to undertake more or less foolish things which I happen to repent more or less.”

 

Vincent had five younger siblings, three sisters and two brothers. The steadfast support of his brother Theo made Vincent’s work possible; Theo died 6 months after Vincent’s suicide. After a failed marriage, Cornelis, the youngest sibling, enlisted as a volunteer in the Boer army in South Africa; he may have committed suicide or been killed in battle. The youngest sister, Wilhelmina, to whom Vincent wrote a series of letters, was interned in a psychiatric asylum at the age of about 35, a few years after Vincent’s death; she was said to suffer from schizophrenia and died in the asylum at the age of 79. His mother, with whom Vincent exchanged occasional letters, lived to the age of 87, surviving not only her husband but all of her sons. Her three sons all died in their 30s, while the three daughters lived into their 70s.

 

Failed Careers and Beginnings as an Artist: At the age of 16, Vincent began to work as an apprentice for an art dealer in a firm founded by an uncle. After 4 years near his family in The Hague, he was transferred to London, where he stayed for 2 years. During that time, he suffered a severe disappointment in his first amorous infatuation and became deeply depressed. For months he remained gloomy, renounced any social life, and communicated little with his family. His thoughts turned increasingly toward religion. As he became more passionately involved in religion, he lost all interest in his job as an art dealer, the financial aspects of which he disdained, and was dismissed by his firm. He devoted the next 4 years to his calling as a preacher. He failed to obtain a formal theology degree and eventually worked as an evangelist in a miserably poor mining district in Belgium. There, he shared his last belongings with his brethren and soon looked dirt poor and black faced himself. His extreme charitable behavior was viewed by his superiors as incompatible with the dignity of an ecclesiastic position. When he refused to moderate his deportment, van Gogh was dismissed by the church; he again suffered a marked depression. To the great distress of his parents, he abandoned the religious beliefs that had sustained him and began to adhere to socialist ideals and agnostic views. “Though I have changed, I am the same,” he wrote in a letter to Theo. “My only anxiety is, how can I be of use in the world?” At the age of 27, he resolved to become an artist with the passion to produce works of art for the people.

 

Largely on his own, van Gogh pursued his new career with singular intensity. He was able to persevere in spite of lack of recognition, thanks to the unfailing financial and moral support from his brother Theo, who had become an art dealer in Paris. The life of van Gogh is well documented through a steady flow of letters to Theo and others.. He experienced his second passionate and ill-fated infatuation with an ardent and incredibly stubborn pursuit of his recently widowed cousin Kee, who scorned him. He then alienated most of his family by living with a prostitute and her two children for over a year. Theo warned Vincent that their father planned to put him in a lunatic asylum. After he returned to live with his parents for a period, Vincent and his father quarreled frequently and violently. He painted Still Life With Bible, in which next to an open bible was the novel La Joie de Vivre, written by the socialist and agnostic Emile Zola. In 1885, his father died suddenly at the door of their home when returning from a walk. Vincent’s devotion to art remained intense all the while.

 

Paris: Onset of Illness: After 6 years as an artist in the Netherlands and Belgium, Vincent joined Theo in Paris for 2 years (1886–1888). There he met many painters who were to become famous, Paul Gauguin among them, and was strongly influenced by the impressionist movement. While in Paris, he began to suffer from minor paroxysms consisting of episodes of sudden terror, peculiar epigastric sensations, and lapses of consciousness. Observers reported occasions of an initial tonic spasm of the hand and a peculiar stare, followed by a confusional-amnestic phase. His use of absinthe, an alcoholic beverage with convulsant properties favored by French artists, appears to have played a crucial role in the precipitation of van Gogh’s illness. He tended to be untidy and quarrelsome; his irascible temper caused many unpleasant scenes and rendered him an undesirable in a number of places. He lived with his brother and often kept him up much of the night with endless disputes. Theo remained sympathetic, yet increasingly felt his brother’s presence a burden. Theo described Vincent in a letter to their younger sister as follows: “It seems as if he were two persons: one, marvelously gifted, tender and refined, the other, egotistic and hard hearted. They present themselves in turns, so that one hears him talk first in one way, then in the other, and always with arguments on both sides. It is a pity that he is his own enemy, for he makes life hard not only for others but also for himself” All along, Vincent persisted in perfecting his art.

 

Provence: A Major Illness Unfolds: When van Gogh left for Arles in southern France early in 1888, he was an accomplished artist, although not recognized and still dependent on regular financial support from Theo, who believed in his genius. He would now create perhaps the most intense paintings ever produced; yet in Arles his illness evolved and reached psychotic dimensions for the first time before the end of 1888.

 

Vincent wrote after his arrival in Arles, “I was surely about to suffer a stroke when I left Paris. It affected me quite a bit when I had stopped drinking and smoking so much, and as I began to think instead of knocking the thoughts from my head. Good heavens, what despair and how much fatigue I felt at that time”. Yet he soon resumed his former habits of using absinthe and cognac. He explained in a letter how he was coping with his state of heightened emotionality: instead of thinking of disastrous possibilities, he would throw himself completely into his work, and “if the storm within gets too loud, I take a glass more to stun myself”. He became more disturbed. Feverish creative activity alternated with episodes of listlessness to the point of exhaustion. Unpredictable mood shifts of dysphoria alternating with euphoria or with “indescribable anguish” became more frequent. Excerpts of letters written after his first breakdown best document his mental states that before had been present to a lesser degree. “I am unable to describe exactly what is the matter with me; now and then there are horrible fits of anxiety, apparently without cause, or otherwise a feeling of emptiness and fatigue in the head.…and at times I have attacks of melancholy and of atrocious remorse” . “There are moments when I am twisted by enthusiasm or madness or prophecy, like a Greek oracle on the tripod. And then I have great readiness of speech” . He became more prone to violent rages and noticed an increasing lack of sexual arousal. He frequently complained of feeling faint and of having “poor circulation” and a “weak stomach.” He continued to write to Theo, often daily, reporting on the creation of his works in precise detail. And he kept painting. When he announced to Theo his first painting of a starry night, he wrote, “It is good for me to work hard. But that does not keep me from having a terrible need of—shall I say the word—yes, of religion. Then I go out at night to paint the stars” Indeed, in a zeal reminiscent of his selfless efforts as an evangelist, he relentlessly devoted himself to create works of art for the people.

 

Vincent felt lonely in Arles and with Theo’s help persuaded Gauguin to join him in the fall of 1888 to establish together a “Studio of the South.” The relationship of the two artists became increasingly quarrelsome, and Vincent wrote, “Our dispute is at times excessively animated like with electricity, at times we end up with tired and empty heads, like an electric battery after discharge.” Gauguin’s visit lasted only 2 months and ended in catastrophe. On Christmas Eve 1888, after Gauguin already had announced he would leave, van Gogh suddenly threw a glass of absinthe in Gauguin’s face, then was brought home and put to bed by his companion. A bizarre sequence of events ensued. When Gauguin left their house, van Gogh followed and approached him with an open razor, was repelled, went home, and cut off part of his left earlobe, which he then presented to Rachel, his favorite prostitute. The police were alerted; he was found unconscious at his home and was hospitalized. There he lapsed into an acute psychotic state with agitation, hallucinations, and delusions that required 3 days of solitary confinement. He retained no memory of his attacks on Gauguin, the self-mutilation, or the early part of his stay at the hospital.

 

His murderous gesture directed against Gauguin was reported by the intended victim in his memoirs. The scandalous event in the house of prostitution and van Gogh’s subsequent hospitalization were recorded in the local press. Some plausible explanations later were offered for the strange happenings. Already psychotic, van Gogh may have carried out the attack on Gauguin driven by hallucinatory command voices and may have cut off part of his own ear in self-punishment for his offensive voices. This psychotic logic was perhaps influenced by van Gogh’s knowledge of the bullfight ritual, in which the matador presents a cut-off ear of the killed bull to a fair lady of his choice.

 

At the hospital, Felix Rey, the young physician attending van Gogh, diagnosed epilepsy and prescribed potassium bromide. Within days, van Gogh recovered from the psychotic state. About 3 weeks after admission, he was able to paint Self-Portrait With Bandaged Ear and Pipe, which shows him in serene composure. At the time of recovery and during the following weeks, he described his own mental state in letters to Theo and his sister Wilhelmina: “The intolerable hallucinations have ceased, in fact have diminished to a simple nightmare, as a result of taking potassium bromide, I believe.” “I am rather well just now, except for a certain undercurrent of vague sadness difficult to explain.” “While I am absolutely calm at the present moment, I may easily relapse into a state of overexcitement on account of fresh mental emotion.” He also noted “three fainting fits without any plausible reason, and without retaining the slightest remembrance of what I felt”

 

After 2 weeks in the hospital, van Gogh was still followed by Dr. Rey but evidently was not sufficiently warned to abstain from absinthe. He suffered another two psychotic episodes with brief hospitalizations. Following the humiliation of being taunted publicly by juveniles and confined to the hospital for the fourth time upon the demand of concerned citizens, van Gogh voluntarily entered the asylum at Saint-Rémy in May 1889. During the full year he remained there, he experienced three psychotic relapses with prominent amnesia, at least twice upon leaves to Arles with resumption of his use of absinthe in the company of old friends and Rachel. Dr. Peyron, an old-fashioned physician who had served in the French navy, was the medical director at Saint-Rémy; he maintained Dr. Rey’s diagnosis of epilepsy but failed to continue treatment with potassium bromide. The last psychotic episode was the most protracted, lasting from February to April 1890; van Gogh experienced terrifying hallucinations and severe agitation. Upon recovery, he complained bitterly of the religious content of his episodes and wished to get away from the nuns who cared for him. While at Saint-Rémy, he produced some 300 works of art, among them several copies of religious scenes by older masters and the transcendental masterpiece Starry Night, which was painted in June 1889.

 

Auvers-sur-Oise: The Suicide: Theo became engaged toward the end of 1888, married 4 months later, and became a father in early 1890. Each event coincided with an exacerbation of van Gogh’s condition; he may have been drinking more whenever he felt that his unique bond with Theo was threatened. Shortly before entering the asylum at Saint-Rémy, Vincent had written to his brother, “And without your friendship I would be driven to suicide without pangs of conscience—and as cowardly as I am, I would finally do it”. Theo had continued to support his brother without fail. Suicidal gestures by Vincent, reported at the time of his initial hospitalization in Arles and during his stay at the asylum, had consisted of ingesting turpentine, paint, or lamp oil and were carried out in a confusional state. Such an episode was described by the painter Signac (who had been permitted to take van Gogh from the hospital in Arles to visit his studio). Signac described van Gogh as being entirely rational until after suffering a minor attack, at which point he put a bottle of turpentine to his mouth and had to be brought back to the hospital.

 

At discharge from the asylum in May 1890, van Gogh was judged cured by his physician. The artist then moved north of Paris to Auvers-sur-Oise, where he spent the last 10 weeks of his life. Theo had recommended Auvers, where van Gogh could live near Paul Gachet, a physician and friend of the artists. He abstained from drinking by now and remained free from seizures and confusional episodes. His art was beginning to gain recognition, and a painting had been sold. But further financial support became uncertain as Theo’s health began to fail. There were some bitter words between the brothers, and Vincent felt himself to be a burden. Still, he worked at a furious pace, completing 70 paintings and 30 drawings during his 70 days at Auvers. The heavenly bodies, so luminous in the past, now were absent from his skies, except for a single peculiar occasion (The White House at Night With Figures and a Star). He painted immense fields of wheat under dark and stormy skies, commenting, “It is not difficult to express here my entire sadness and extreme loneliness”. In one of his last paintings, Wheat Field With Crows, the black birds fly in a starless sky, and three paths lead nowhere. He borrowed a gun from his innkeeper “to scare the crows away” when he was painting. There still was another episode of fury directed at Dr. Gachet, who had failed to frame a painting by Guillaumain as van Gogh had demanded. Vincent gestured toward the gun in his pocket, but he walked away. In his last letter sent to Theo, he mentioned that he wanted to replenish his stock of paint and asked for help to this end. Three days later, on a Sunday, Vincent shot himself in the lower chest or upper belly in a field outside Auvers. “I couldn’t stick it any longer, so I shot myself,” he told a friend. He died 2 days later with Theo next to him. It has been assumed that his Field With Stacks of Wheat, a bright picture of grain harvested and sheaved, may have been his very last – a symbol of work completed.

 

Epilogue: An analysis of van Gogh’s illness and emotionality must not obscure the fact that the great artist also had great strengths.. Apart from distinct episodes of madness when he used absinthe and had seizures, he maintained a remarkable degree of lucidity during his stormy life, as is well documented in his letters. Vincent remained marvelously creative until his death. He did not paint during his major crises except during the last prolonged episode at Saint-Rémy. There he painted, before full recovery, a few canvases from memory, which he referred to as “reminiscences of the North.” Jan Hulsker pointed out that these paintings are the only works of his entire voluminous oeuvre to show signs of a transient mental collapse.

 

Almost invariably, van Gogh drew and painted from nature. The influence of his exceptional emotional and spiritual intensity on his art is most evident when van Gogh deviated from the depiction of natural scenes, particularly in the rendering of the sky, in several of his masterpieces. He had confessed to a “terrible need for religion” when he painted his first picture of a starry night (over the river Rhone) in September 1888. Starry Night, painted in June 1889 at Saint-Rémy, is undoubtedly van Gogh’s most mysterious picture. The artist, usually so verbal, never revealed the origin of his scene of a spectacularly transfigured sky. Tralbaut. commented on Starry Night, “The fire that smoldered within him and broke out in hallucinations of the senses has here been set down on canvas in a most striking fashion.” With this painting, van Gogh may have immortalized his memory of a particularly haunting and perhaps recurrent vision of apocalyptic dimension experienced during a twilight state. The vision is set in the familiar surroundings of the soft hills and flame-shaped cypresses of Provence, and yet the village with its church spire is reminiscent of van Gogh’s native Brabant. He seems to be telling us, “This is where I come from, this is where I am now, and here is my universe of overpowering storms.”

 

The illness of van Gogh has perplexed 20th-century physicians, as is evident from the nearly 30 different diagnoses that have been offered, from lead poisoning or Meniere’s disease to a wide variety of psychiatric disorders. Many writers have acknowledged the epilepsy but considered the psychiatric disorder an independent mental illness. Monroe recognized the unique episodicity of van Gogh’s mental changes, the role of absinthe in his illness, and an underlying epileptoid limbic dysfunction that was associated with his creativity but also, if overly intense, would render him ill. Earlier, in an exceptionally well-documented study, Gastaut reasoned that the artist’s psychiatric changes were based on temporal lobe epilepsy produced by the use of absinthe in the presence of an early limbic lesion.

 

Earlier in his life, van Gogh experienced two prolonged episodes of reactive depression. Both episodes were followed by a prolonged period of hypomanic or even manic behavior: first as evangelist to the poor miners in Belgium and then as the quarrelsome and overly talkative artist in exciting Paris. The major illness of his last 2 years developed in the presence of seizures, and its nature has remained controversial. The known details of his psychiatric illness will be reviewed together with what is known about the psychopathology of individuals with epilepsy, and differential diagnostic considerations will follow.

 

Views of Gastaut and the Earlier French Physicians: Felix Rey, the young physician who attended van Gogh in Arles and diagnosed his epilepsy, was familiar with the psychiatric aspects of epilepsy as they were taught in France during the second half of the 19th century. In fact, Aussoleil, a medical school companion of Felix Rey, wrote a dissertation on larvate epilepsy and worked nearby when van Gogh was admitted to the hospital in Arles. In 1860, Morel listed the symptoms that were to be so prominent in van Gogh’s illness:

 

Under the term larvate epilepsy I have described a variant of epilepsy which does not reveal itself by the actual minor or major attacks, but on the contrary by all the other symptoms which accompany or precede ordinary epilepsy characterized by seizures, that is: periodic alternation of excitement and depression; manifestations as it were of sudden fury without sufficient grounds and for most trivial reasons; a usually most irritable disposition; amnesia, as usually occurs in epilepsy, of dangerous acts carried out during momentary or transient rages. Some epileptics of this type have even experienced genuine auditory and visual hallucinations.

 

Morel had already recognized the highly conscientious (hypersocial) disposition of such patients that contrasted strikingly with their proneness to outbursts of violent anger.

 

Gastaut pointed out that premodern psychiatrists who had studied institutionalized patients with epilepsy chiefly had observed individuals with mesial temporal sclerosis, as documented by their neuropathologic studies. His findings linked premodern psychiatric views of epilepsy to modern epileptology. Gastaut published his study of van Gogh in 1956, after he had conducted a series of investigations on carefully selected groups of patients with different forms of epilepsy. He documented that certain behavioral and emotional changes among patients with epilepsy were specifically related to mesial (limbic) temporal lobe epilepsy: episodic irritability contrasting with an otherwise hypersocial disposition, slow-adhesive (viscous) personality traits, and a global hyposexuality. This temporal lobe syndrome associated with epilepsy was manifest in van Gogh.

 

Gastaut recognized the crucial role of absinthe in the manifestation of van Gogh’s major psychiatric symptoms. By his own confession, van Gogh required “a glass too much” to numb his inner storms when they became too intense. The artist was not known to become intoxicated and may not have been drinking more than many of his contemporaries, but he was particularly vulnerable to the epileptogenic properties of absinthe, the favorite drink of the French artists of his time. Oil of wormwood (from the herb Artemisia absinthium) constitutes the toxic principle of the alcoholic drink absinthe. Wormwood oil contains the terpene compound thujone, a structural isomer of camphor. Both thujone and camphor induce convulsions and were used during the 1920s and 1930s in the study of models for epilepsy; von Meduna considered the use of thujone for the convulsive therapy of schizophrenia before using camphor. In 1873, Magnan described for the first time what he termed épilepsie absinthique, and later neurologic textbooks of the period referred to the relationship of absinthe and epilepsy. In the early part of the 20th century, absinthe became outlawed in most countries because of its psychotoxic effects.

 

During his stay in Paris, where he was introduced to absinthe, van Gogh developed complex partial seizures with gradual accentuation of partially preexisting emotional and behavioral changes. In most patients with temporal lobe epilepsy, psychiatric changes tend to occur only gradually and in a less violent form. In van Gogh, perhaps because of an early temporal-limbic lesion, these changes became fully evident soon, characterized by heightened emotionality with the opposite poles of irritability and hyperethical or hyperreligious trends, by meticulous attention to detail and stubborn persistence in speech and writing (viscosity), and by hyposexuality.. His seizures and his psychotic episodes were precipitated by the use of absinthe and stopped once he abstained.

 

Modern Concepts of the Neuropsychiatric Disorders of Epilepsy: The presence of seizures, the intermittent and pleomorphic symptoms of the interictal phase, the prolonged amnestic-confusional psychotic episodes at the height of van Gogh’s illness, and, finally, the profile of his personality traits all suggest a diagnosis of epilepsy-related illness.

 

There has been fair agreement among experts about the personality traits observable among patients with epilepsy. Vincent’s viscosity was manifest by his intense clinging to people he loved, his persevering on details, and a tendency to debate endlessly and to write excessively. Gastaut viewed viscosity as the characteristic core trait of an individual with temporal lobe epilepsy. Gastaut also pointed out how van Gogh’s hypersocial, spiritual, and even hyperreligious personality contrasted sharply with his episodes of anger to the point of fury, a conflict that other authors have considered the dynamic core issue in patients with epilepsy and heightened emotionality.

 

Before becoming an artist, van Gogh had been devoted to a religious career for years and had served as an utterly selfless evangelist; religious motives later reemerged in his artwork. Yet his episodic rages are well documented, became notorious once he used absinthe, and reached a peak with his acute illness and the murderous gesture directed at Gauguin. He represents an example of the heightened conflict between fury and atonement – good and evil forces – that has so often been noted among individuals afflicted with epilepsy. Paroxysmal episodes of irritability to the point of rage on the one hand and a (remorseful) highly ethical, selfless, helpful, and often hyperreligious disposition on the other had been noted by observers before Gastaut, from Morel and Kraepelin to Freud and Szondi.

 

Suicidal attempts infrequently may be carried out in a state of acute postictal depression.. The artist’s earlier suicide attempts probably had been of this nature and were not consciously planned. In patients with interictal dysphoric disorder, the moods of euphoria tend to be brief, their depressive moods more prominent. With the latter comes a suicidal risk that is 4–25-fold higher among patients with epilepsy over the rate in the general population and is particularly associated with chronic temporal lobe epilepsy.. Suicide tends to occur, peculiarly, at a time when a long-standing seizure disorder has been brought into remission and often comes as a surprise.

 

Supported by his brother Theo, van Gogh had lived for his art. Theo was the one person in his life who had faith in Vincent’s extraordinary accomplishments and had been, in fact, the lifeline throughout his career as an artist. With Theo’s support threatened, the storm within became less bearable. When considering the forward-looking tone of his last letter to Theo, Hulsker had no doubt that the suicidal act resulted from a momentary impulse.. For the last few months of his life, van Gogh had abstained from absinthe and was free from both seizures and psychosis. Depressive moods were more prevalent, although not persistent. His productivity had been unbroken in Auvers, and his suicide was not anticipated by those who knew him. It seems to have occurred with a final attack of melancholy, resulting from a still persistent dysphoric disorder. One needs to remember, however, that van Gogh had experienced marked depressive episodes before his seizure disorder.

 

Differential Diagnostic Considerations: Several authors have offered a tentative diagnosis of schizophrenia for van Gogh. In view of both the absence of any of the fundamental symptoms of the disorder and the presence of psychotic episodes with amnestic-confusional features and complete recovery, this diagnosis appears improbable, in spite of the fact that late-onset schizophrenia was diagnosed in one of his sisters.

 

The diagnosis of neurosyphilis has to be considered in view of van Gogh’s lifestyle (he was treated for gonorrhea in 1882), the prevalence of the disease at the time, and its diverse symptoms. However, none of the relatively specific symptoms of the disease was ever noted. Above all, this diagnosis is unlikely, since he did not show any persistent impairment of mental or somatic functions.

 

Following two major disappointments (an unrequited early love and a failed career as an evangelist), van Gogh clearly experienced prolonged episodes of depression; both events preceded major career changes. He also experienced sustained periods of hypomania or mania. His career as an evangelist ended when he developed a sort of altruistic religious mania. A bipolar history of prolonged periods of extremely high levels of energy, enthusiasm, and productivity alternating with episodes of depression is not uncommon among writers and artists, and the hypomanic phase is often not identified.. The artist’s increasingly elevated mood during his exciting stay in Paris probably was a factor in his use of absinthe, the substance that precipitated his second major illness.

 

Vincent experienced seizures only after his use of absinthe with its convulsant property. He never experienced generalized seizures but had only partial seizures, suggesting the presence of a latent epileptogenic zone, most likely in the mesial-temporal area, that was activated by his use of absinthe. As postulated by Gastaut, a perinatal brain lesion may have resulted in van Gogh’s severe reaction to absinthe: the partial seizures, the marked interictal dysphoric disorder, and the psychotic episodes with prominent amnesia. When he became increasingly ill during the last 2 years of his life, van Gogh did not experience any of the sustained mood changes characteristic of bipolar disorder. Instead, he experienced sudden and brief changes of depressive mood, elation, anxiety, or fury, and his intense artistic efforts were frequently disrupted by episodes of listlessness; these intermittent pleomorphic changes developed after onset of seizures and are specific for the dysphoric disorder of epilepsy.

 

While interictal dysphoric disorder and psychosis tend to become manifest after an interval of years following onset of epilepsy, there are also patients with dysphoric or epileptoid traits in the absence of overt seizures; these patients often have identifiable subtle brain lesions. The existence of an epileptoid temperament analogous to schizoid or cyclothymic temperaments, before or independent of the respective major illness, was often debated in the premodern psychiatric literature when epilepsy was a major topic. The early intense emotionality of van Gogh, with the contrasting poles of explosive irritability on the one hand and goodness and religiosity on the other, may be considered an expression of this temperament independent from his cyclothymic disposition.

 

Vincent van Gogh’s suicide may have been an unexpected event, perhaps precipitated by a dysphoric mood; remission of the seizures may have favored the final depressive event. But when he had recovered from his severe illness upon discharge from the asylum, the support from his brother, upon whom he had depended totally for his career as an artist, had become seriously threatened. Although the artist had been able to remain productive, a depressive mood had become more evident. In the past, he had reacted to crucial losses with marked depression, and this illness probably was the main factor in his death.

 

 

Starry Night Painting, Oil on Canvas, Saint-Rémy, France: June, 1889

Prospective Study of Statin Use and Risk of Parkinson Disease

 

According to article published in the Archives of Neurology (2012;69:380-384), a study was performed to prospectively examine whether use of statins is associated with altered risk of Parkinson disease (PD).

 

The study included 38,192 men and 90,874 women participating in 2 ongoing US cohorts, the Health Professional Follow-up Study and the Nurses’ Health Study. Information on regular cholesterol-lowering drug use (2x/week) was collected in 1994 in both cohorts via questionnaire. Relative risks (RRs) and 95% CIs were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, duration of hypercholesterolemia, and other covariates. The main outcome measure was Incident PD.

 

Results showed that during 12 years of follow-up (1994-2006), 644 incident PD cases (338 women and 306 men) were documented. The risk of PD was lower among current statin users (adjusted pooled RR = 0.74; P = 0.049) relative to non-users. A significant association was observed in participants younger than 60 years at baseline (adjusted pooled RR = 0.31; P = 0.02) but not among those who were older (adjusted pooled RR = 0.83; P = 0.25) (P for interaction = 0.03).

 

According to the authors, regular use of statins was associated with a modest reduction in PD risk and the possibility that some statins may reduce PD risk deserves further consideration.

Brain Imaging Study Finds Evidence of Basis for Caregiving Impulse

 

According to an article published in Neuroimage (2012;60:884-93), distinct patterns of activity, which may indicate a predisposition to care for infants, appear in the brains of adults who view an image of an infant face, even when the child is not theirs. The findings raise the possibility that studying this activity will yield insights not only into the caregiver response, but also when the response fails, such as in instances of child neglect or abuse.

 

While the study recorded participants’ brain activity, the participants did not speak or move during the imaging sessions. Yet their brain activity was typical of patterns preceding such actions as picking up or talking to an infant. The activity pattern could represent a biological impulse that governs adults’ interactions with small children. From their study results, the authors concluded that this pattern is specific to seeing human infants since the pattern did not appear when the participants looked at photos of adults or of animals, and even baby animals.

 

For the study, the authors showed seven men and nine women a series of images while recording their brain activity with a functional magnetic resonance imaging scanner. In the scanner, participants viewed images of puppy and kitten faces, full-grown dogs and cats, human infants and adults. When the areas and strength of brain activity were compared in response to each kind of image, they found that infant images evoked more activity than any of the other images in brain areas associated with three main functions:

 

Premotor and Preverbal Activity -The study documented increased activity in the premotor cortex and the supplemental motor area, which are regions of the brain directly under the crown of the head. These regions orchestrate brain impulses preceding speech and movement but before movement takes place.

 

Facial Recognition – Activity in the fusiform gyrus – on each side of the brain, about where the ears are – is associated with processing of information about faces. Activity the researchers detected in the fusiform gyrus may indicate heightened attention to the movement and expressions on an infant’s face, the researchers said.

 

Emotion and Reward – Activity deep in the brain areas known as the insula and the cingulate cortex indicated emotional arousal, empathy, attachment and feelings linked to motivation and reward, the researchers said. Other studies have documented a similar pattern of activity in the brains of parents responding to their own infants.

 

Participants also rated how they felt when viewing adult and infant faces. They reported feeling more willing to approach, smile at, and communicate with an infant than an adult. They also recorded feeling happier when viewing images of infants.

 

Taken together, the authors contended that the findings suggest a readiness to interact with infants that previously has been only inferred, and only from parents. Such brain activity in nonparents could indicate that the biological makeup of humans includes a mechanism to ensure that infants survive and receive the care they need to grow and develop.

Nearly 800,000 Deaths Prevented Due to Declines in Smoking

 

Since the first Surgeon General’s report on smoking and health in 1964, tobacco control efforts in the United States have included restrictions on smoking in public places, increases in cigarette excise taxes, limits on underage access to cigarettes, and efforts to increase public awareness of the hazards of smoking. Now, according to a published online in the Journal of the National Cancer Institute (14 March 2012), 20th century tobacco control programs and policies are responsible for preventing more than 795,000 lung cancer deaths in the United States from 1975 through 2000.

 

According to the authors, if all cigarette smoking in this country had ceased following the release of the first Surgeon General’s report, a total of 2.5 million people would have been spared from death due to lung cancer in the 36 years following that report.

 

The study, which is part of the NCI-sponsored Cancer Intervention and Surveillance Modeling Network (CISNET), utilized a comparative modeling approach in which detailed cigarette smoking histories for individuals born from 1890 through 1970 were constructed, and then related the histories to lung cancer mortality in mathematical models. Using these models, the study was able to estimate the impact of changes in smoking patterns resulting from tobacco control activities on lung cancer deaths during the period from 1975 through 2000.

 

The study created three scenarios for evaluation. In the first scenario, called actual tobacco control, data were used on actual smoking behaviors of men and women in the United States. The second scenario, called no tobacco control, predicted smoking behaviors that would have existed if no tobacco control policies were put in place. In the third scenario, called complete tobacco control, the authors examined the possible outcome if all smoking in the United States had ceased as of 1965, the first full year after the 1964 Surgeon General’s Report on Smoking and Health was released.

 

Results showed that the difference between lung cancer deaths in the no tobacco control scenario and the numbers of actual lung cancer deaths provided an estimate of the numbers of lung cancer deaths averted as a result of tobacco control activities. The authors estimated that, without tobacco control programs and policies, an additional 552,000 men and 243,000 women would have died of lung cancer in the period from 1975 through 2000.

 

Similarly, the difference between the no tobacco control scenario and the complete tobacco control scenario provided an estimate of the lung cancer deaths that could have been avoided if everyone who smoked quit in 1965 and no one started smoking. If tobacco control efforts had been completely successful, an additional 1.7 million lung cancer deaths would have been averted from 1975 – 2000. In total, if all smoking had ceased completely in 1965, as many as 2.5 million fewer people would have died from lung cancer (1.6 million men and 883,000 women).

 

The estimations only run through the year 2000 because, for more recent years, sufficiently detailed data were unavailable when the project began. However, it can be inferred that additional lung cancer deaths have been averted since the year 2000, because according to previous research, smoking rates among U.S. adults have continued to fall, dropping from 23.2 percent in 2000 to 20.6 percent in 2008, and leveling off in recent years. Previous research indicates that much of the decrease in smoking rates can be attributed to tobacco control policies. In addition, although beyond the scope of the journal article, rates of other smoking related cancers, and smoking-related diseases, such as cardiovascular and respiratory diseases, have declined due to tobacco control programs and policies.

 

CISNET is a consortium of NCI-sponsored investigators who use statistical modeling to improve our understanding of cancer control interventions in prevention, screening, and treatment. This modeling approach, which has been validated in several previous studies, can be used to guide public health research and priorities. The network is working on a project to study the efficacy of lung cancer screening for smokers in different age and exposure level groups, based on the results of benefit for spiral CT screening found in the NLST for heavy smokers.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area

 

FDA Proposes Lower Risk Classification for Certain Tuberculosis Tests

 

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis that usually attacks the lungs. People infected with TB who also have weakened immune systems are at much higher risk for developing the disease, and the disease can be fatal if left untreated. The disease is a leading killer of people with HIV worldwide. Not everyone infected with TB develops the disease, and only people with disease can spread TB. Common signs and symptoms of TB disease include: a bad cough lasting three weeks or longer, chest pain, coughing up blood, weakness and fatigue, and weight loss.

 

Nucleic acid-based tuberculosis tests can detect the presence of copies of tuberculosis bacterium genetic materials (RNA or DNA) in a mucus (sputum) sample obtained from the patient. This allows timely identification of TB disease and can shorten the time needed to diagnose TB disease from one to two weeks to one to two hours. When used in conjunction with other clinical tests, nucleic acid-based tests can result in earlier treatment, improved patient outcomes, and interrupt further spread of TB. Currently, these tests are Class III (high-risk) devices that require the more rigorous pre-market approval application. In proposing to down-classify to Class II (moderate-risk), the FDA also issued a draft guidance for manufacturers that identifies the risks associated with false positive and false negative test results, the risks to health care workers handling specimens, and makes recommendations on how to mitigate those risks. The rule would allow manufacturers to utilize the faster, more streamlined clearance pathway for medical devices.

 

The Centers for Disease Control and Prevention (CDC) recommends health care providers perform nucleic acid testing on at least one sample of mucus coughed up from the lower airways (sputum) from patients with signs and symptoms of TB disease, when the test result would alter patient treatment or TB control activities.

 

The FDA is seeking public input on the draft guidance for 90 days. Comments can be submitted online or in writing to: Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

The Pre-Existing Condition Insurance Plan – Success or Boondoggle?

 

By Mark L. Horn, MD, MPH, Chief Medical Officer, Target Health Inc.

 

 

A progress report from the Center for Consumer Information and Insurance Oversight (CCIIO) on an element of the Affordable Care Act (ACA) was issued this week and seemed to attract less attention than typically accrues to ACA matters. Perhaps some have forgotten, but the ACA created a temporary mechanism for uninsured patients with pre-existing conditions to secure health coverage prior to 2014 when the ACA established Insurance Exchanges, mandating that all insurers cover pre-existing conditions, become operational. The idea is straightforward, there are many Americans who, due to job loss, disability, financial distress or simple bad luck find themselves uninsured, and among this group there is a doubly unfortunate segment that has a pre-existing significant health problem. This combination of events creates a potentially unsolvable and financially ruinous problem, uninsurable health costs.

 

Since this dilemma, widely known and lamented, was intensively discussed during the health reform debates, it’s surprising that this report has not received more attention. The program, labeled the Pre-Existing Condition Insurance Plan (PCIP) is operational, and will have enrolled nearly 50,000 people in either federally or state run (it is structured on a ‘Federalist’ model) PCIPs through December, 2011.

 

The demographics of the enrollees suggest that the program has attracted, as presumably was anticipated, individuals who for a variety of reasons are unable to secure employer coverage and are too young for Medicare, a population long recognized as especially vulnerable to the coverage ‘cracks’ in our health system. Among medical needs covered, and specifically cited in the report, are cancer, circulatory disorders, and rehabilitative care including “certain forms of radiation and chemotherapy”. Among criticisms: the current anticipated cost of coverage, nearly $29,000 per member/per year, is significantly higher than the $13,000 estimated in November 2010. The report notes that this reflects the significant and severe medical needs of this especially vulnerable population.

 

What are we to make of this?

 

To this observer, it is hard to call this anything but a success. A highly vulnerable population without viable insurance options has been defined, and a mechanism of insuring them at rational premiums (e.g. prices they can manage) has been devised. There is no suggestion in the report that the cost overruns emanate from anything other than legitimate medical expenses; finally, coverage, while ‘actuarially’ subsidized is not free, e.g. premiums are charged and paid.

 

This seems a particularly American solution, effective, pragmatic, (and imperfect), to a serious social problem affecting a clearly vulnerable group of people. Its imperfections are non-trivial, among these its expense; nevertheless for many it apparently successfully addresses a critical problem. As citizens, we should be proud of, and grateful for, this success.

Meeting – Risk-Based Approaches to Clinical Investigations

 

Target Health Inc. is pleased to announce that Dr. Jules T. Mitchel and Mr. Dean Gittleman will be presenting a Case Study on “Analyzing the Potential of Transforming Clinical Trials through Risk-Based Monitoring,” at CBI’s Meeting on Risk-Based Approaches to Clinical Investigations – Data Quality, Operational and Technological Considerations. The meeting will be held on April 10-11, 2012 at the Doubletree Hotel Center City, Philadelphia, PA. Our colleagues from Bristol-Myers Squibb, Johnson & Johnson, Vertex, Teva, Endo, Otsuka and more will be presenting.

 

As a valued reader of On Target, CBI is offering $400 off of your registration fee. Just enter priority code XPM636 when registering at www.cbinet.com/clinicalinvestigations.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com

Profound Reorganization in Brains of Adults Who Stutter: Auditory-Motor Integration Located in Different Part of Brain

 

In adults who have stuttered since childhood the processes of auditory-motor integration are indeed located in a different part of the brain to those in adults who do not stutter, new research shows. (Credit: marksykes / Fotolia)

 

 

Hearing Beethoven while reciting Shakespeare can suppress even a King’s stutter, as recently illustrated in the movie “The King’s Speech.” This dramatic but short-lived effect of hiding the sound of one’s own 1) ___speech indicates that the integration of 1) ___hearing and motor functions plays some role in the fluency (or dysfluency) of speech. New research has shown that in adults who have stuttered since childhood, the processes of auditory-motor integration are indeed located in a different part of the 2) ___brain to those in adults who do not stutter.

 

Dr. Nicole Neef and Dr. Martin Sommer from the University of Goettingen, together with Dr. Bettina Pollok from the University of Duesseldorf, studied the performance of a group of adults who stutter, as well as a control group of adults who do not stutter, in a finger tapping exercise. They used Transcranial Magnetic Stimulation TMS 3) ___ ___ ___ to interfere temporarily with brain activity in the dorsolateral premotor cortex while the participants tapped their fingers in time with the clicks of a metronome. In control subjects, disturbing the left premotor cortex impaired the finger tapping, but disturbing the right premotor cortex had no effect. In stuttering adults, the pattern was reversed: the accuracy of finger tapping was affected by disturbing the right hemisphere, and unaffected when disturbing the 4) ___left.

 

Previous research has already linked stuttering with a right-shifted cerebral 5) ___blood flow in the motor and premotor areas during speech. In this new study, a shift of auditory-motor integration to the right side of the brain occurred even in a task not directly involving speech. Thus, in the brains of adults who stutter there appears to be a profound reorganization possibly compensating for subtle white matter disturbances in other parts of the brain — the left inferior frontal regions. These findings shed light on the extent of the 6) ___reorganization of brain functions in persistent developmental stuttering.

 

ANSWERS: 1) speech; 2) brain; 3) Transcranial Magnetic Stimulation; 4) left; 5) blood; 6) reorganization

Beethoven Unlikely to Have Died from Lead Exposure

 

 

Antique 19th-century engraving of a portrait of Ludwig van Beethoven. The German composer and pianist was born on December 17, 1770 in Bonn, Germany, he died on March 26, 1827 in Vienna, Austria. (Credit: iStockphoto)

 

 

Less than a year ago, a researcher at Mount Sinai School of Medicine measured the amount of lead in two skull fragments of Ludwig van Beethoven and found that it was unlikely for lead poisoning to have caused the renal failure that was partly responsible for Beethoven’s death, eliminating one of the many suggested causes of death for the famed composer. As much as 95% of lead in the adult body is stored in bone, where it stays for years, even after death,” said Andrew Todd, PhD, Associate Professor of Preventive Medicine, Mount Sinai School of Medicine. “Measuring the amount of lead in Beethoven’s bone fragments allows us to reach back through time to measure his lead exposure during life.”

 

Skull fragments from Beethoven were examined using a technique called x-ray fluorescence (XRF). XRF does not damage or destroy the sample and has been used by Dr. Todd in many studies of the human health effects of lead. A very small radiation dose (about the same dose as 10 minutes of natural background radiation) is used to make the lead stored in bone give off x-rays, which are recorded in a radiation detector. The larger skull fragment was found by Dr. Todd to have 12 micrograms of lead per gram of bone mineral. “For someone who was Beethoven’s age, we would expect more than that; one comparison dataset predicts 21 micrograms of lead per gram of bone mineral,” said Dr. Todd.

 

Lead exposure is known to cause irritability, for which Beethoven was renowned, as well as colic and kidney failure, from which, along with liver failure, Beethoven is thought to have died. Currently two dozen or more health issues have been suggested for Beethoven, some of them deadly. This work largely rules out one of them. Work done in 2000 at the Argonne National Laboratory examined only the surface of the small fragment of Beethoven’s bone that Dr. Todd also tested. Dr. Todd’s work also examined the complete thickness of a much larger fragment of Beethoven’s skull. According to Dr. Todd, there have been many explanations put forward about Beethoven’s death. Some have found high lead levels in Beethoven’s hair, which can show lead exposure only from the last several months of his life. According to a researcher in Vienna, that reading could have reflected the treatment used to heal a wound from surgery Beethoven underwent in an attempt to save his life. Such treatment in those days consisted of salves that might have contained lead. Dr. Todd’s bone measurements quantify lead over Beethoven’s entire lifetime. Others have theorized that Beethoven had high lead exposure from the long used practice of sweetening the cheapest wine with lead. But, those theories have been disputed based on records Beethoven kept when he became deaf which showed he had the resources to buy more expensive wines.

 

The skull fragments Dr. Todd measured are thought to have been obtained the first time Beethoven was reburied (in 1863) by a physician, Gerhard von Breuning, who as a boy had been a friend of Beethoven’s and who was a comfort to him in his last months. Dr. von Breuning is thought to have given the fragments to Romeo Seligmann (the first Professor of the History of Medicine at the University in Vienna) in whose family they have remained. The above story is reprinted from materials provided by Mount Sinai School of Medicine.

 

For your listening pleasure, below, one of the most perfect, glorious pieces of music ever written played by Daniel Barenboim – Joyce Hays, Target Health Inc.

 

Beethoven Piano Sonata “Pathetique” First Movement

 

Beethoven Piano Sonata “Pathetique” Second Movement

 

Beethoven Piano Sonata “Pathetique” Third Movement

 

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