General paresis, also known as general paralysis of the insane (GPI), paralytic dementia, or syphilitic paresis is a severe

neuropsychiatric Neuropsychiatry or Organic Psychiatry is a branch of medicine that deals with psychiatry as it relates to neurology, in an effort to understand and attribute behavior to the interaction of neurobiology and social psychology factors. Within neurop ...

disorder, classified as an organic mental disorder and is caused by late-stage

syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and ...

and the chronic

meningoencephalitis Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the menin ...

and

cerebral atrophy Cerebral atrophy is a common feature of many of the diseases that affect the brain. Atrophy of any tissue means a decrement in the size of the cell, which can be due to progressive loss of cytoplasmic proteins. In brain tissue, atrophy describes ...

that are associated with this late stage of the disease when left untreated. GPI differs from mere

paresis In medicine, paresis () is a condition typified by a weakness of voluntary movement, or by partial loss of voluntary movement or by impaired movement. When used without qualifiers, it usually refers to the limbs, but it can also be used to desc ...

, as mere paresis can result from multiple other causes and usually does not affect cognitive function. Degenerative changes caused by GPI are associated primarily with the frontal and temporal lobar cortex. The disease affects approximately 7% of individuals infected with syphilis, and is far more common in third world countries where fewer options for timely treatment are available. It is more common among men. GPI was originally considered to be a type of madness due to a dissolute character, when first identified in the early 19th century. The condition's connection with syphilis was discovered in the late 1880s. Progressively, with the discovery of organic arsenicals such as

Salvarsan Arsphenamine, also known as Salvarsan or compound 606, is a drug that was introduced at the beginning of the 1910s as the first effective treatment for syphilis, relapsing fever, and African trypanosomiasis. This organoarsenic compound was the fi ...

and Neosalvarsan (1910s), the development of

pyrotherapy Pyrotherapy (artificial fever) is a method of treatment by raising the body temperature or sustaining an elevated body temperature using a fever. In general, the body temperature was maintained at 41 °C (105 °F). Many diseases were t ...

(1920s), and the widespread availability and use of

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum usin ...

in the treatment of syphilis (1940s), the condition was rendered avoidable and curable. Prior to this, GPI was inevitably fatal, and it accounted for as much as 25% of the primary diagnoses for residents in public psychiatric hospitals.

Signs and symptoms

Symptoms of the disease first appear from 10 to 30 years after infection. Incipient GPI is usually manifested by

neurasthenic Neurasthenia (from the Ancient Greek νεῦρον ''neuron'' "nerve" and ἀσθενής ''asthenés'' "weak") is a term that was first used at least as early as 1829 for a mechanical weakness of the nerves and became a major diagnosis in North A ...

difficulties, such as fatigue, headaches, insomnia, dizziness, etc. As the disease progresses, mental deterioration and personality changes occur. Typical symptoms include loss of social inhibitions, asocial behavior, gradual impairment of judgment, concentration and short-term memory,

euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

mania Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wi ...

, depression, or

apathy Apathy is a lack of feeling, emotion, interest, or concern about something. It is a state of indifference, or the suppression of emotions such as concern, excitement, motivation, or passion. An apathetic individual has an absence of interes ...

. Subtle shivering, minor defects in speech and

Argyll Robertson pupil Argyll Robertson pupils (AR pupils) are bilateral small pupils that reduce in size on a near object (i.e., they accommodate), but do ''not'' constrict when exposed to bright light (i.e., they do not react). They are a highly specific sign of neu ...

may become noticeable.

Delusion A delusion is a false fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or some ...

s, common as the illness progresses, tend to be poorly systematized and absurd. They can be grandiose, melancholic, or paranoid. These delusions include ideas of great wealth, immortality, thousands of lovers, unfathomable power, apocalypsis, nihilism, self-guilt, self-blame, or bizarre hypochondriacal complaints. Later, the patient experiences

dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effectively ...

intention tremor Intention tremor is a dyskinetic disorder characterized by a broad, coarse, and low frequency (below 5 Hz) tremor evident during deliberate and visually-guided movement (hence the name intention tremor). An intention tremor is usually perpendi ...

hyperreflexia Hyperreflexia is overactive or overresponsive bodily reflexes. Examples of this include twitching and spastic tendencies, which indicate upper disease of the upper motor neurons and the lessening or loss of control ordinarily exerted by higher ...

myoclonic Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...

jerks, confusion, seizures and severe muscular deterioration. Eventually, the paretic dies bedridden, cachectic and completely disoriented, frequently in a state of

status epilepticus Status epilepticus (SE), or status seizure, is a single seizure lasting more than 5 minutes or 2 or more seizures within a 5-minute period without the person returning to normal between them. Previous definitions used a 30-minute time limit. The s ...

Diagnosis

The diagnosis could be differentiated from other known psychoses and dementias by a characteristic abnormality in eye pupil reflexes (

), and, eventually, the development of muscular reflex abnormalities,

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

s, memory impairment (

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affec ...

) and other signs of relatively pervasive neurocerebral deterioration. Definitive diagnosis is based on the analysis of cerebrospinal fluid and tests for syphilis.

Prognosis

Although there were recorded cases of remission of the symptoms, especially if they had not passed beyond the stage of psychosis, these individuals almost invariably experienced relapse within a few months to a few years. Otherwise, the patient was seldom able to return home because of the complexity, severity and unmanageability of the evolving symptom picture. Eventually, the patient would become completely incapacitated, bed ridden, and would die, the process taking about three to five years on average.

History

While retrospective studies have found earlier instances of what may have been the same disorder, the first clearly identified examples of paresis among the insane were described in Paris after the

Napoleonic Wars The Napoleonic Wars (1803–1815) were a series of major global conflicts pitting the French Empire and its allies, led by Napoleon I, against a fluctuating array of European states formed into various coalitions. It produced a period of Fren ...

. General paresis of the insane was first described as a distinct disease in 1822 by Antoine Laurent Jesse Bayle. General paresis most often struck people (men far more frequently than women) between 20 and 40 years of age. By 1877, for example, the superintendent of an asylum for men in New York reported that in his institution this disorder accounted for more than 12% of admissions and more than 2% of deaths. Originally, the cause was believed to be an inherent weakness of character or constitution. While

Friedrich von Esmarch Johannes Friedrich August von Esmarch (9 January 1823 – 23 February 1908) was a German surgeon. He developed the Esmarch bandage and founded the ''Deutscher Samariter-Verein'', the predecessor of the '' Deutscher Samariter-Bund''. Life E ...

and the psychiatrist had asserted as early as 1857 that

caused general paresis (progressive Paralyse), progress toward the general acceptance by the medical community of this idea was only accomplished later by the eminent 19th Century syphilographer

Jean Alfred Fournier Jean Alfred Fournier () (21 May 1832 – 25 December 1914) was a French dermatologist who specialized in the study of venereal disease. Biography As a young man he served as an interne at the Hôpital du Midi as an understudy to Philippe Rico ...

(18321914). In 1913 all doubt about the syphilitic nature of paresis was finally eliminated when

Hideyo Noguchi , also known as , was a prominent Japanese bacteriologist who in 1911 discovered the agent of syphilis as the cause of progressive paralytic disease. Early life Noguchi Hideyo whose childhood name was Seisaku Noguchi was born to a family of farme ...

and J. W. Moore demonstrated the syphilitic

spirochaete A spirochaete () or spirochete is a member of the phylum Spirochaetota (), (synonym Spirochaetes) which contains distinctive diderm (double-membrane) gram-negative bacteria, most of which have long, helically coiled (corkscrew-shaped or s ...

s in the brains of paretics. In 1917

Julius Wagner-Jauregg Julius Wagner-Jauregg (; 7 March 1857 – 27 September 1940) was an Austrian physician, who won the Nobel Prize in Physiology or Medicine in 1927, and is the first psychiatrist to have done so. His Nobel award was "for his discovery of the therapeu ...

discovered that malaria therapy (in this case, medical induction of a fever) involving infecting paretic patients with

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects humans and other animals. Malaria causes Signs and symptoms, symptoms that typically include fever, fatigue (medical), tiredness, vomiting, and headaches. In se ...

could halt the progression of general paresis. He won a

Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...

for this discovery in 1927. After World War II the use of

to treat syphilis made general paresis a rarity: even patients manifesting early symptoms of actual general paresis were capable of full recovery with a course of penicillin. The disorder is now virtually unknown outside

developing countries A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agree ...

, and even there the epidemiology is substantially reduced. Some notable cases of general paresis: * General

Ranald S. Mackenzie Ranald Slidell Mackenzie, also called Bad Hand, (July 27, 1840 – January 19, 1889) was a career United States Army officer and general in the Union Army during the American Civil War. He was described by General Ulysses S. Grant as i ...

was retired from the US Army in 1884 for "general paresis of the insane" 5 years before his death in 1889. * Theo Van Gogh, brother of painter

Vincent van Gogh Vincent Willem van Gogh (; 30 March 185329 July 1890) was a Dutch Post-Impressionist painter who posthumously became one of the most famous and influential figures in Western art history. In a decade, he created about 2,100 artworks, inclu ...

, died six months after Vincent in 1891 from "dementia parylitica" or what is now called syphilitic paresis. * The Chicago gangster

Al Capone Alphonse Gabriel Capone (; January 17, 1899 – January 25, 1947), sometimes known by the nickname "Scarface", was an American gangster and businessman who attained notoriety during the Prohibition era as the co-founder and boss of the ...

died of syphilitic paresis, having contracted syphilis in a brothel in 1919, and not having been properly treated for it in time to prevent his later onset of syphilitic paresis.

References

External links