Pioneers in Neurology

Alois Alzheimer | Jean-Martin Charcot | Auguste Deter | John Langdon Down | George Huntington | Friedrich Heinrich Lewy | James Parkinson | Arnold Pick


Alois_AlzheimerAlois Alzheimer  1864 – 1915

Alois Alzheimer, a German psychiatrist, was appointed Director of the State Asylum in Frankfurt am Main in 1895.  His research was focused on understanding the cerebral cortex and pathology of the human brain.  In 1901, a woman named Auguste Deter entered his clinic.  The 51-year old patient was suffering from strange behavioral symptoms plus the loss of short-term memory. His evaluation revealed that she was suffering from dementia, which means “deprived of mind.”  In 1903, Dr. Alzheimer moved to another clinic in Munich but continued to follow the case of Auguste Deter.  Working with two Italian physicians, Gaetano Perusini and Francesco Bonfiglio, novel staining techniques would be used to discover that her brain contained two lesions called amyloid plaques and neurofibrillary tangles.

On 3 November 1906, Dr. Alzheimer presented a lecture describing an “unusual disease of the cerebral cortex” which affected a woman in her fifties and caused memory loss, disorientation, hallucinations, and ultimately death.  This was the first time the pathology and the clinical symptoms of presenile dementia would be presented together.  The disorder was named “Alzheimer’s disease” by Emil Kraeplin, who was Alzheimer’s director at the Munich clinic.

Today, over 5.4 million Americans have Alzheimer’s disease, including over 588,000 in California and 75,000 residents of Orange County.  Age is the most significant risk factor, with 5% of the population over 65 afflicted and the incidence doubling every five years thereafter.  Presently, there is no cure for Alzheimer’s disease.

Jean-Martin-CharcotJean-Martin Charcot  1825 — 1893

Jean-Martin Charcot was a French neurologist and professor of anatomical pathology.  Charcot is known as the “father of modern neurology” and his name is associated with at least 15 medical disorders.  For 33 years, he worked and taught at the famous Salpêtrière Hospital where his reputation as an instructor drew much attention.  In 1868, he named and was the first to describe multiple sclerosis, an autoimmune disease in which the body’s immune response attacks a person’s central nervous system, leading to demyelination.  Multiple sclerosis usually begins in young adulthood and is more common in females.  It has a prevalence that ranges between 2 and 150 per 100,000 individuals.

Charcot also was the first to describe Charcot-Marie-Tooth disease, a heterogeneous inherited neuropathy characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms in the advanced stages.  Charcot described and named amyotrophic lateral sclerosis (ALS), a fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movements.  ALS is sometimes called Charcot’s disease but more commonly known as Lou Gehrig’s disease.

Charcot’s work greatly influenced the developing fields of neurology and psychology.  He was the foremost neurologist of late nineteenth century France and has been called “the Napoleon of the neuroses.”  His students included Sigmund Freud, William James, and Georges Gilles de la Tourette.  Charcot also coined the name Parkinson’s disease after he further described this condition.  Finally, he is also credited with introducing geriatrics as a separate educational specialty.

Auguste-DeterAuguste Deter  1850 — 1906

Auguste was married to Karl Deter and during the late 1890s she began to show unusual symptoms, including memory loss and delusions.  On 25 November 1901, Karl had his 51-year old wife admitted to the Frankfurt Mental Institution where she was examined by Dr. Alois Alzheimer.  Her frequent loss of memory caused her to remark, “I have lost myself.”  Mrs. Deter would become Dr. Alzheimer’s obsession over the coming years.  In April 1906, she died and Alzheimer had her records and brain sent to Munich, Germany where he was working in the laboratory of Dr. Emil Kraepelin.  With the assistance of two Italian physicians, Alzheimer used special staining techniques and found that Mrs. Deter’s brain contained two lesions, amyloid plaques and neurofibrillary tangles.  Even today, plaques and tangles are the diagnostic hallmarks for Alzheimer’s disease.  Mrs. Deter will forever be known in the annals of medicine as being the first person to be recognized with a specific form of dementia that we now refer to as Alzheimer’s disease.

Dementia (meaning “deprived of mind”) is a non-specific syndrome (set of signs and symptoms) in which memory and one or more other cognitive domains, such as attention, language, and problem solving are impaired severely enough to interfere with everyday functioning.  Dementia is usually progressive, resulting in long-term decline in cognitive function due to damage or disease beyond what might be expected from normal aging. Although dementia is far more common in the geriatric population, it may occur in any stage of adulthood.

Alzheimer’s disease is the most common cause of dementia, although not all cases of dementia are due to Alzheimer’s disease.  Other causes of dementia include Lewy body dementia, frontotemporal dementia, vascular dementia, and Parkinson’s disease dementia.  Treatment options vary depending on the type of dementia affecting an individual.

John-Langdon-DownJohn Langdon Down  1828 —1896

John Langdon Down was a British physician who showed great devotion to science and medicine, working in organic chemistry early on and later winning awards for physiology and graduating at the top of his class at Royal London Hospital Medical College.  Much to the dismay of Down’s professors, he chose to take a position as medical superintendent at Earlswood Institution for the Mentally Retarded in Surrey.  Given Down’s academic excellence, many were surprised by his choice not to take a more prestigious position.  Though Down later took on other prominent positions, including as a lecturer on therapeutics and principles of medicine at London Hospital Medical College, he always held a significant role in the organization and functioning of Earlswood, which would become a blueprint for future care of the mentally ill in the United Kingdom.

In 1866, Down published the first English description of the condition that would ultimately bear his name. Nearly 93 years before the chromosome finding of trisomy 21 was published, Langdon Down gave a complete description of the phenotype of individuals with this common developmental disability.  In 1959, Jérôme Lejeune identified Down syndrome as a chromosome 21 trisomy.

Down syndrome is associated with impaired cognitive ability and physical growth as well as altered facial appearance.  The intellectual disability is typically mild to moderate, however, in a few cases can be severe to profound.  The incidence of Down syndrome is estimated at 1 per 800 to 1,000 births and much more common among older mothers. Because the Alzheimer’s APP gene is located on chromosome 21, almost all individuals with Down syndrome will go on to develop Alzheimer’s disease by the 5th decade of life.

George-HuntingtonGeorge Huntington  1850 – 1916

George Huntington was an American physician who followed in his father’s and grandfather’s footsteps as a family doctor in East Hampton, Long Island.  Together their 78-year period of observing families in the community provided a unique perspective.  In 1872, at age 22 and just one year out of medical school, Huntington published his landmark description of Huntington’s disease, “On Chorea,” which drew international recognition in accurately and graphically providing the classic definition of this disorder.  The cardinal features of Huntington’s disease were recognized in his description, particularly the hereditary nature, adult onset, progressive course and fatal outcome.

As Huntington noted:

“The hereditary chorea, as I shall call it, is confined to certain and fortunately a few families, and has been transmitted to them, an heirloom from generations away back in the dim past.  It is spoken of by those in whose veins the seeds of the disease are known to exist, with a kind of horror, and not at all alluded to except through dire necessity, when it is mentioned as ‘that disorder.  It is attended generally by all the symptoms of common chorea, only in an aggravated degree, hardly ever manifesting itself until adult or middle life, and then coming on gradually but surely, increasing by degrees, and often occupying years in development, until the hapless sufferer is but a quivering wreck of his former self.”

Friedrich-Heinrich-LewyFriedrich Heinrich Lewy  1885 – 1950

Friedrich Heinrich Lewy was born in Berlin in 1995.  He was the son of a Jewish physician and followed in his father’s footsteps, studying medicine in Berlin and Zurich.  After obtaining his medical degree in 1910, Lewy worked at the Neuropsychiatric Laboratory in Munich with colleagues – such as Emil Kraepelin, Alois Alzheimer, and Franz Nissi – who became equally famous.  During this time, Lewy began studying the morphology of Parkinson’s disease.  In his initial publications of 1912 and 1913, Lewy was the first to describe the pathological anatomy of Parkinson’s disease.  His exhaustive description was based on the analysis of 85 patients, who he personally examined, both clinically and physiologically, and results of their post-mortem examinations.  In his initial reports, Lewy described the neuronal inclusions which would later be called “Lewy bodies” in 1919 by Tretiakoff.  Lewy bodies are neuronal inclusions present in areas of neurodegeneration in Parkinson’s disease.  Late in the 20th century, Lewy bodies were also observed in cortical areas of dementia patients, leading to the clinical and pathological description of what is now known as 
Lewy body dementia.  It is the second leading cause of dementia in the elderly, accounting for 20% of all cases.  Lewy body dementia can occur in a pure form or in conjunction with other brain pathologies, such as those of Parkinson’s or Alzheimer’s disease.

Lewy held many prestigious positions in his career, eventually becoming the director of the Neurological Research Institute and Clinic in Berlin in 1932.  His time as director was short-lived as he was dismissed from the position by the Nazi regime in 1933.  Following his dismissal, Lewy left Germany, living for a short time in England and then moving to the United States.  During his time in America, he changed his name to Frederic Henry Lewy.  Interestingly, in his lifetime, Lewy failed to understand the significance Lewy bodies would have for Parkinson’s disease and later for Lewy body dementia.

James-ParkinsonJames Parkinson  1755 – 1824

James Parkinson, an English physician, was the first to describe the movement disorder that would later bear his name.  His 1817 paper entitled “An Essay on the Shaking Palsy” described six individuals with palsy that he did not examine directly but observed during their daily walks.  Others had previously written about the so-called shaking palsy, including the ancient Greek doctor Galen. Parkinson’s description, however, was so comprehensive that over 60 years after his publication, Jean Martin Charcot coined the term “Parkinson’s disease” to describe the condition afflicting these patients.  In his essay, Parkinson noted:

“The first symptoms perceived are, a slight sense of weakness, with a proneness to trembling in some particular part . . . but most importantly in one of hands and arms. As the disorder progressed, patients were forced to lean forward while walking, so much so that . . . being at the same time, irresistibly impelled to take much quicker and shorter steps, and thereby to adopt unwillingly a running pace. Still later, the tremors made even sleep difficult. It now seldom leaves him for a moment; but even when exhausted nature seizes a small portion of sleep, the motion becomes so violent as not only to shake the bed-hangings, but even the floor and sashes of the room.”

Today, Parkinson’s disease is recognized as the second most common neurodegenerative disorder after Alzheimer’s disease, with over 1 million Americans affected.  It is characterized by muscle rigidity, resting tremor, and bradykinesia resulting from a loss of dopaminergic neurons in the substantia nigra.

Arnold-PickArnold Pick  1851-1924

Arnold Pick was born in 1851 to Austrian parents.  He attended medical school in Vienna and graduated in 1875.  He became a full professor at the University of Prague in 1886.  He also spent time working at the Prague Asylum and was known for taking extremely detailed case reports and histories, even from difficult patients.  From 1892-1896, Pick published a series of papers on patients with aphasia (loss of the ability to understand or express speech) and apraxia (inability to execute learned, purposeful movements) associated with focal cortical atrophy.  Interestingly, Pick did not view these cases as representing a new disease but instead believed that the patients were suffering from a form of senile dementia.   It was Alois Alzheimer who later drew attention to Pick’s papers when he observed similar cases but found they had distinctive histopathology.  Alzheimer noted the characteristic inclusions that would later be called Pick’s bodies and the swollen cells, which would be known as Pick’s cells.  It was in 1922 when Gans first suggested the name “Pick’s atrophy” and the term “Pick’s disease” was introduced by Onari and Spatz in 1925.

Once used to describe a specific group of clinical symptoms, the term “Pick’s disease” now refers primarily to a disease with Pick’s bodies.  Pick’s disease is one of the causes of frontotemporal lobar degeneration, which has three subtypes.  Pick’s disease pathology is more often associated with two of the subtypes, frontotemporal dementia and progressive nonfluent aphasia than the third subtype, semantic dementia.

Pick studied diverse topics, including aphasia, apraxia, and memory, while at the Prague asylum.  His achievements are particularly notable considering the social and political turmoil during his time in Prague.  Pick died in 1924 from sepsis after a medical procedure.


 

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