Dementia paralytica

General paresis of the insane (GPI), also known as dementia paralytica, is a disease that most young doctors have never seen and most likely will never see. It has almost completely disappeared, yet occupies a prominent place in the history of medicine. During the greater part of the nineteenth century and well into the twentieth, it was the most common dementing neurological disease known to man, frequent and feared, accounting at one time for up to 20% of admissions to mental institutions. At its peak it claimed the lives of many notable celebrities such as Schumann, Donizetti, Guy de Maupassant; and it features prominently in the writings of Sir Arthur Connan Doyle, AJ Cronin, Agatha Christie, and Somerset Maugham.

The disease was first seen in the mental hospitals of Paris shortly after the Napoleonic wars, but whether the large movements of troops and populations during those years had anything to do with it remains unclear. Characterized by dementia and paresis, it appeared to be a new disease, although isolated cases may have been seen in England as far back as 1672. It was first characterized as a French disease, but soon spread to other countries and became one of the most common diseases in mental asylums. At first the medical authorities of the time, especially in France, had difficulty in reconciling the coexistence of symptoms that were clearly organic with those comfortably fitted into the classifications of psychiatric disorders prevalent at the time.

Not surprisingly then, the first complete clinical and pathological description of the disease (by Antoine Laurent Jesse Bayle in 1822) was not well-received by the French medical establishment. It ran counter to the then accepted classification of mental disorders into such categories as for example monomania; and it was even thought at the time that the cause of some psychiatric disorders resided in the intestines. Bayle was young, only 22 years old, perhaps over enthusiastic, possibly arrogant, and his style provoked his critics to react violently. Some of his opponents regarded his views as speculative assertions, vague, inconsistent, or unoriginal. A long controversy ensued; and eventually Bayle retired from psychiatry and medicine, becoming a librarian and bibliographer. Yet his insistence that insanity may be due to pathological changes in the brain has been called the most important single achievement in the history of mental disease.  In the years that followed his description other investigators confirmed his observations, but for a long time the cause of general paresis remained a mystery.

From its early appearance to recent times, the symptoms of the disease remained characteristic, reducing its victims within a few months to utter physical dissolution and complete dementia. Delusions of grandeur and immense wealth featured prominently. Common pebbles were transformed into gems, as one clinical description had it. Patients talked about their grandiose schemes and the immense wealth it had brought them. Some would be distributing money lavishly. One such patient, reported in 1885, excited, sleepless, prodigal in his expenses, deluded about his greatness and wealth, thought himself Pope and Emperor of Germany. Guy de Maupassant claimed to be the younger son of the Virgin Mary; planted twigs into the soil of his garden to produce his offsprings; retained his urine because it contained diamonds; later would howl like a dog and lick the walls of his cell. Patients became restless, talking incessantly, then violent and destructive, tearing everything into shreds. Lying on their bed or in a padded cell, still happy in their delusion of splendor, they lost all contact with the external world, until horribly wasted and emaciated to the extreme they would succumb to paralysis or coma.

Among the many prominent victims of the disease was Lord Randolph Churchill, father of Winston Churchill, a flamboyant and controversial Conservative politician, notorious womanizer, gambler, and financial speculator. Brilliant, ambitious, and energetic, he held several important cabinet posts but during the 1880s began to behave erratically in a manner that seemed to exaggerate his previous character. Exhibiting frantic bouts of activity and violent rages alternating with periods of withdrawal and apathy, he was first thought to be suffering from nervous exhaustion, but then developed unsteadiness, indistinct speech, and memory lapses leading to some painfully embarrassing performances in parliament. During his periods of delusional euphoria he would outline extravagant plans for a great future, then his outrageous behavior worsened, he became increasingly debilitated and died in 1895.

But what could cause this horrible and uniformly fatal disease? By the late 1870s general paresis had virtually unanimously been accepted as a disease in its own right, disentangled from the morass of other neurologic and psychiatric illnesses. But the relation to syphilis was slow to be recognized and even slower to be accepted. It began with clinical observations in England by physicians such as Esmarch and Jessen (1857), this occurring at the time when on the Continent the natural history of syphilis was being better described and understood and in France venereology had become a profession in its own right distinct from dermatology. During the late nineteenth century Jean Alfred Fournier, a prominent venereologist, vigorously promoted the link between syphilis and general paresis in a series of important publications. In England the neuropathologist Frederick Mott (1853 – 1926) played an important role in bringing about the acceptance that general paresis was due to an infection. Yet by the turn of the century, many authorities continued to question the primary role of syphilis, while admitting it was a great “predisposing factor,” but considering trauma, alcoholism, nervous stress and strain, or mental overexertion and work as exciting factors, not even ruling out respiratory or intestinal autointoxication as possible factors in other “unexplained cases.” Others considered dementia paralytica to be a meningo-encephalitis of unknown cause or a degenerative disease of the nerve fibers.

With the advent of the new century, however, things began to change rapidly. In Berlin in 1905, the microbiologist Schaudinn and the venereologist Hoffmann announced they had observed a pale, fragile spirochete associated with syphilitic lesions. Though resistant to laboratory culture and not fulfilling Koch’s postulates, Treponema pallidum became rapidly accepted as the primary cause of syphilis. Within a short period of time the Bavarian immunologist Wasserman and his team developed a successful complement fixation test that allowed the diagnosis of syphilis by laboratory tests. By 1908 the Wasserman reaction had entered into everyday practice and revolutionized the medical understanding of syphilis. But the issue was not settled until 1913, when Noguchi and Moore demonstrated the presence of the causative organism, Treponema pallidum, in the brain of afflicted patients. There were later advances, such as when in 1917 Julius Wagner-Jauregg was able to halt the progression of the disease by infecting patients with malaria. During most of the first part of the twentieth century the standard treatment of syphilis consisted of drugs such as arsenic, supplemented by the induction of fever by malaria or electrical means. Then came the revolution, the discovery of penicillin. At first it was shown that could arrest the early symptoms of cerebral syphilis, but eventually neurosyphilis largely disappeared. It is nowadays almost never seen, especially not in developed countries, but its history constitutes an interesting and dramatic example of how the natural history of diseases and our understanding of them changes over the centuries.

 


George Dunea, MD, Editor-in-Chief (Summer 2013)

Highlighted in Frontispiece Summer 2013 – Volume 5, Issue 3