Medicine: The Riddle of Tle

A hard-to-diagnose malady causing bizarre behavior may be curable

MEDICINE:

ARTHUR CREW INMAN was a native of Atlanta who, following a physical and emotional breakdown in 1916, at the age of twenty-one, left college and retired to a darkened, soundproof suite of apartments in Boston. Bedridden for the most part, he was attended by servants, physicians, and strangers whom he paid to talk to him. An inheritance supported this life-style. He complained of crippling aches and pains, extreme sensitivity to light and sound, and despair over the state of the world. Something compelled him to record these complaints and much more in a personal diary that he kept daily for more than forty years. He attempted suicide several times and in 1963 succeeded, after noise from the construction of a skyscraper drove him wild. He left behind a 155-volume, 17-million-word diary—probably the longest ever written—which, greatly abridged, was published as The Inman Diary in 1985, in two volumes, by Harvard University Press.

The question is, What was wrong with Inman? Physicians who saw him— including “thirty-four eminent doctors” who examined him after his breakdown— concluded unanimously that he had no apparent physical ailment. Inman, convinced that his difficulties had an organic source, rejected the medical establishment and resigned himself to the care of osteopaths. But even his chief osteopath, who is given the name “Dr. Frederick Lakian" in the published diary, and who treated him for twentyfive years, says, “Arthur was a hypochondriac. To a great degree, his symptoms were purely imaginary.” Why, then, did he live the way he did? What made him so susceptible to pain and depression, so driven to write?

A disorder that could explain all of Inman’s difficulties does exist. It is temporal lobe, or temporolimbic, epilepsy (TLE), an often disabling neurological disorder. TLE is manifested by bizarre sensory and somatic seizures that can be triggered by light and sound. In some patients TLE is accompanied by hypergraphia, a compulsive urge to write detailed diaries and poems— and sometimes to draw with similar intensity.

The most common form of epilepsy among adults, TLE is believed to affect 600,000 to a million Americans. Some doctors speculate that if TLE were properly diagnosed, it might be found to affect one in a hundred adults—making it an extremely common illness. Like other epilepsies, it is the result of electrical storms in the brain: abnormal, excessive firing of neurons in the central nervous system. Epilepsy can be caused by congenital abnormalities, tumors, viruses, and injuries to the brain, but most cases of epilepsy are idiopathic: their cause is unknown. Doctors call TLE a complex partial seizure disorder—“complex” because its seizures usually result in impairment but not cessation of consciousness, and “partial" because they involve only part of the brain and body. This terminology distinguishes the disorder from the better-known grand-mal and petit-mal epilepsies, in which seizures are “generalized” throughout the brain and cause either unconsciousness and gross motor convulsions or brief lapses in awareness.

Many historical figures may have had TLE, including such religious and political leaders as Moses, Mohammed, Julius Caesar, and Alexander the Great, and such writers as Dostoyevsky, Flaubert, Lewis Carroll, and Eugene O’Neill. Another possible TLE sufferer is Vincent van Gogh, whose hypergraphia is well documented. In a fifteenmonth period in the late 1880s, for example, van Gogh produced hundreds of paintings, drawings, and lengthy letters. The conversion of another great writer of letters, the Apostle Paul, on the road to Damascus, had several of the hallmarks of a complex partial seizure—a blinding flash of light, confusion, a disembodied voice, and subsequent loss of appetite.

In a typical complex partial seizure a person stares blankly, smacks his lips or swallows, performs an automatic motion such as shaking a limb or picking at clothing, and is then bewildered and unable to speak for several minutes. But variations abound. The brain structures that can be affected by TLE are so heterogeneous— they control the senses, memory, learning, heart rate, and blood pressure—that a seizure can be experienced in any number of ways. Physical changes, such as irregular heartheat and sexual climax, can occur. Some patients report intense emotions—fear, for example, that “something terrible is about to happen,” or tremendous, unexplained joy. Dostoyevsky wrote, “I would not exchange for all the happiness life could give me the bliss” that preceded his seizures. Others experience a particular vivid memory every time they have a seizure. Still others enter into a “dreamy state,” in which their emotions and memory are temporarily shut off. Altered sensory states are common. They include the “Alice in Wonderland syndrome,” in which objects appear shrunken or enlarged; auditory and visual hallucinations; and “depersonalization”—the feeling of being outside or above one’s body. Some seizures are preceded by pain, nausea, a foul smell of “burning rubber” or “dead skunk,” or a “funny feeling” in the chest or stomach. Inappropriate laughter or crying may follow seizures. Many patients sleep for several hours afterward and then feel better.

More even than with most diseases, deciding whether or not someone has TLE is like doing detective work. To diagnose TLE, doctors look for an apparent clinical seizure as well as a “spike focus”—a region of the brain where abnormal electrical discharges begin, detectable on an electroencephalogram (EEG). TLE seizures are often not recognized for what they are, and large areas of the temporal lobes are inaccessible to the EEG. So although a positive EEG during a clinical seizure is the best indicator of TLE, a negative EEG does not rule it out. Only in the past ten years have medical researchers been able to use sophisticated diagnostic tools such as EEGs with electrodes that can be implanted inside the brain or on its surface. These techniques, however, are expensive and still not widely used. As a result, many people with TLE (including roughly 30 percent of those with TLE being treated at the Beth Israel Hospital, in Boston) are first misdiagnosed as having a psychiatric disorder. The prevalence of psychosis seems much greater in people with TLE than in the general population, however, for reasons that are not yet known.

IN INMAN’S CASE, the best evidence is in the diary. The EEG was not invented until 1929, long after Inman swore off medical science, so he never had one. His scanty hospital records and autopsy report are unrevealing. But his description of his 1916 breakdown, which involved bizarre sensory and emotional states and culminated in an attack while he was at the home of friends, is consistent with a TLE seizure. “My whole nervous system went on strike,” Inman wrote.

Specks of light zigzagged in front of me. My ears whistled. . . . The room began to circle with a curious rotary motion, very bewildering. I heard them talking, asking questions, but my ears were full of noise, and I could not understand. Suddenly. . . I began to cry long, racking sobs, without any end.

His friends were frightened and tried to put him to bed. After lying down for a while, Inman was able to join them for dinner.

This was the first of many such attacks. Inman wrote in 1919, “I feel as though I were undergoing a change such as occurs in a violin string when the pitch is raised. This condition has occurred to me time after time. . . .” Thirty years later he wrote,

I live in a box where the camera shutter is out of order and the filter doesn’t work and the film is oversensitive, and whatever that is beautiful or lovely by rights registers painfully or askew. . . . The simplest factors of existence, sunlight and sound, uneven surfaces, moderate distances, transgress my ineffective barriers and raid the very inner keep of my broken fortifications, so that there exists no sanctuary or fastness to which I can withdraw my sensitivity, neither awake nor asleep.

A medical report appended to the published diary suggests that the 1916 breakdown could have resulted from a viral infection, such as mononucleosis. But since no fever was reported, a virus is unlikely. Inman’s sensitivities to light and sound and his visual and auditory hallucinations suggest migraine headaches as well as TLE. Migraines, thought to result from the expanding and shrinking of blood vessels to the brain, are more complex than other headaches. They share symptoms with TLE, including nausea, numbness, and temporary speech difficulties. Migraines are much more common among epilepsy sufferers than in the general population, and have on occasion responded well to treatment with anticonvulsant drugs. Inman probably had migraines. “But migraines alone could not have accounted for his unusual personality,”says Shahram Khoshbin, a neurologist at Harvard Medical School and the Brigham and Women’s Hospital, in Boston. “TLE could have.”

PEOPLE WITH TLE, according to Khoshbin, tend to demonstrate five interictal traits (that is, traits in evidence between rather than during seizures). The first of the traits is hypergraphia. The second is hyperreligiosity—an unusual degree of concern with morality, philosophy, and mysticism, sometimes leading to multiple religious conversions. The third is “stickiness,”or clinginess. People with this trait are often reluctant to end conversations. Doctors say their patients with TLE characteristically prolong appointments by returning to or repeatedly telephoning their offices. The fourth trait is altered or decreased interest in sex. The fifth is aggressiveness— usually undirected and transient, and rarely leading to violence.

The prevalence of this interictal behavior syndrome in people with TLE is controversial. No hard figures exist, and estimates vary widely. Some people with TLE do not have any of the traits. But “a large proportion" of them have some, according to Paul Spiers, a neuropsychologist at the Beth Israel. David Bear, the director of neuropsychiatry at the Vanderbilt University School of Medicine, agrees that the syndrome “could be very common.” Bear says that he finds the syndrome in “a large percentage" of his TLE patients, many of whom are referred to him because of his interest in behavior change and epilepsy. However, Thomas Browne, a neurologist at the Boston University Medical Center and the Veterans Administration Medical Center in Boston, says that in his experience the syndrome occurs in a “minority" of people with TLE—by his estimate, some five to 30 percent.

Pierre Gloor, a neurologist at the Montreal Neurological Institute, known throughout the world as a last stop for “untreatable" epilepsy patients, says that the syndrome may not be apparent unless doctors search for it. “It hits you in the eye in less than ten percent of cases, but that doesn’t mean it doesn’t exist in a somewhat hidden form in some other patients. Sometimes you have to dig for it.”

When the behavior syndrome does occur, it is likely to arise abruptly and uncharacteristically. Researchers at the Beth Israel report the case of an athletic instructor with no previous intellectual interests who became consumed with the idea of writing something important. Another patient there, a middle-aged, semi-literate laborer, “started to keep a minute-by-minute log of his feelings and their relationship to God.”Sexual changes occur just as suddenly. The most common is the loss of interest in sex, notable because it is not accompanied by loss of sexual function. Other patients undergo changes in sexual orientation—for example, alternating between homosexuality and heterosexuality as the frequency of their seizures changes. Though rare, deviant sexual practices—pederasty, bestiality, and fetishism— have also been reported. An extreme example of this is a man with TLE who became sexually aroused only at the sight of a safety pin, an involuntary response that must have resulted from faulty wiring in the brain.

THE NEUROLOGICAI. mechanism underlying the behavior syndrome is not clearly understood. The late Norman Geschwind, a renowned behavioral neurologist at Harvard, hypothesized that the syndrome occurs not as a result of seizures but rather as a consequence of changes in the brain which can themselves cause seizures. Too many and too rapid electrical connections in the brain’s temporolimbic structures may bring about the behavior changes. David Bear calls these brain structures “gatekeepers to consciousness,”for in them the sensory world meets our emotions and relates our sensory experience to biological drives (aggression, fear, hunger, and sexuality). If the structures are damaged, these connections can be altered, producing what Geschwind called “an excessive investment of the environment with limbic significance.” As a result,

external stimuli begin to take on great importance; this leads in turn to increased concern with philosophical, religious, and cosmic matters. Since all events become charged with importance, the patients frequently resort to recording them in written form at great length and in highly charged language.

Many neurologists, however, consider the behavior syndrome questionable— and even pernicious—as a diagnostic category. Robert Feldman, the chief of neurology at the Boston UniversityMedical Center and the Veterans Administration Medical Center in Boston, says that although some patients with TLE “do exhibit these personality traits, serious questions still exist about how specific they are” for TLE. Feldman speculates that the syndrome results not from neurological changes in the brain, as Geschwind proposed, but from the psychological and social stresses that all epilepsy sufferers experience. Seizures often “interfere with interpretation of environmental cues,” he says, adding that people whose seizure disorders began in childhood tend to have the greatest social maladaptation. But the neurologist Martin Albert, also of the Boston University and Boston VA medical centers, is not convinced that the behavior syndrome is entirely the result of external factors. “Children with serious chronic illnesses other than epilepsy are also excluded and stigmatized,” he says. “Why don’t they develop this cluster of traits?”

Many people resist the notion that abnormally bring neurons can alter behavior and emotions. As Paul Spiers explains this resistance, “Who wants to think that a great literary work is based on a disease?” Some doctors, acknowledging the long history of prejudice against people with epilepsy, oppose publicly linking certain personality traits with TLE. That association, according to Thomas Browne, puts an additional and unnecessary burden on people who “already have enough trouble getting along in our society.” David Coulter, the chief of pediatric neurology at the Boston University School of Medicine, says, “The behavior syndrome is a personality disorder, a cluster of pejorative attributes, and gives people with epilepsy a bad name.”

But doctors may do their patients a greater disservice by denying that the behavior syndrome is related to TLE. “The fact is that patients who have these symptoms go around wondering, ‘Am I crazy?”’ Paul Spiers says. “We can say, ‘No, you’re not crazy.”’ Bear emphasizes that the syndrome represents a behavioral change, not a disease. Many of its traits, such as an interest in cosmic issues or a tendency to write extensively, are not in themselves signs of sickness. Dostoyevsky may have written as much and as well as he did because of epilepsy, Spiers says. “One of my TLE patients is a published poet who says that when her seizures are under control, the muse leaves her.”

As FOR INMAN, clearly he had many, if not all, of the traits of the behavior syndrome. On a questionnaire designed by Bear and the psychologist Paul Fedio, of the National Institutes of Health, to determine the extent to which the syndrome is present in patients, Inman scores well within the range of people with TLE and substantially above the control groups. The questionnaire was filled out for Inman separately by Bear and by Libby Smith, one of the editors of The Inman Diary. Smith, who spent seven years reviewing the unabridged diary and interviewing scores of people who knew its author, had never heard of TLE. Both she and Bear gave Inman high marks in nearly all of the eighteen traits listed on the questionnaire. (Together these eighteen make up a personality pattern quite similar to that described by Khoshbin’s five traits.) “Compulsive attention to detail,” for example, describes Inman’s need to make lists and keep to rigid schedules. His childlike charm and tendency to fly into rages translate into high scores in several categories: “dependence,” “deepening of all emotions,”“humorlessness,” and “paranoia.” And his effort to chronicle his era demonstrates his “grandiosity” and “sense of personal destiny.”

The syndrome could explain many of Inman’s peculiarities—which bewildered his diary’s readers. A story recounted by his chief osteopath reads like a textbook definition of stickiness. “I would be sailing off Cape Cod,” Lakian recalls.

The Coast Guard cutter would come up. They’d say they had just had a flash that Arthur Inman wanted to see me immediately. I’d have to call him, ship-to-shore, and tell him I couldn’t come right away. He’d say, “You have to come.” I’d tell him it would cost him a lot of money. He’d say, “I don’t care. Just come.”

Lakian’s description of Inman’s sexual behavior fits the syndrome equally well. “Often when I came to see him, he would be sitting in a rocking chair, with these kids—young girls—in his lap, fondling them, his hands up their legs.”

Sex held a somewhat intellectual fascination for Inman. He liked to lie naked in bed with women. He begged them to describe their sexual feelings to him. But he disliked sexual intercourse, and rarely engaged in it. Even if Inman didn’t have epilepsy, “he must have had some kind of temporal-lobe or limbic disorder,” according to Paul Spiers. “He was both detached and intense—in some sense not emotionally connected to the world.”

Experts caution that the presence of the interictal behavior syndrome is not sufficient grounds for a diagnosis of TLE. But when the syndrome is present, epilepsy may reasonably be considered. Other possible causes of these traits are repeated use of LSD or cocaine, severe depression, and manicdepressive illness.

IF INMAN DID have TLE and were alive today, he would probably be treated with anticonvulsant medications and supportive psychotherapy and perhaps with surgery. Although Inman was never suspected of having epilepsy, he was in fact addicted to two drugs originally used as anticonvulsants—potassium bromide, first used for this purpose in 1859 and now largely discontinued, and barbiturates, introduced early in this century and still regarded as effective. The most common anticonvulsant drugs used today for TLE are carbamazepine, phenytoin, and phenobarbitol. These may eliminate seizures or significantly reduce their frequency and severity in some patients, but have not been shown to affect interictal behavior and do not adequately control seizures for many people with TLE—25 percent of them according to doctors, and roughly 65 percent according to the patients themselves.

After exhaustive two-year surgical work-ups, a small number of TLE patients undergo surgery to remove the part of the brain containing the seizure focus—often a mass of tissue as large as a fist. This operation has been performed, in conjunction with the EEG, on more than 5,000 patients since 1939, and far fewer than one percent have died as a result, largely because patients are not anesthetized during the procedure. Roughly 40 percent of survivors have become seizure-free and able to go off anti-convulsants. Another 40 percent have had significantly fewer seizures while remaining on drugs, and roughly 20 percent have remained the same or worsened. Worsening usually means more-frequent seizures and the introduction of new kinds of seizures, and rarely it involves lasting difficulties with thinking and remembering. Remarkably, however, a common long-term aftereffect of the surgery is improved neurological functioning overall; many patients’ IQs have actually increased, and their moods have heightened. This is probably because epileptic brain tissue interferes with normal brain function.

TLE and the interictal behavior syndrome no doubt deserve much more attention and research. Because the disorder crosses the traditional boundaries between psychiatry and neurology, improved methods of recognizing and treating it may lead to a revolution in the diagnosis and treatment of psychiatric disorders such as manic-depressive illness and schizophrenia. Indeed, some doctors now suspect that many psychiatric disorders are themselves somehow related to seizures. Not long before his death, in 1984, Norman Geschwind wrote,

Behavioral change in temporal lobe epilepsy deserves very special consideration, since it is probably the only cause of major change in behavior for which we have a plausible mechanism of pathogenesis. . . . The importance of this syndrome results from its clinical fascination, its frequency, and from its unique capacity to present to us a clear-cut physiological paradigm for the occurrence of behavioral change after alterations in the brain.

TLE, which permits psychiatrists and neurologists to examine the same problems, may advance knowledge in both fields and lead to a better understanding of the physiological causes of mental illness and mental health.

—Eve LaPlante