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1.
Charcot  J-M De la sclérose latérale amyotrophique. Prog Med.1874;2:325-327, 341-342, 453-455.
2.
Tyler  HRShefner  J Amyotrophic lateral sclerosis. Handb Clin Neurol.1991;15:169-215.
3.
Goldblatt  D Motor neuron disease: historical introduction.  In: Norris  FH Jr, Kurland  LT, eds.Motor Neuron Disease. New York, NY: Grune & Stratton; 1968:3-11.
4.
Charcot  J-M Charcot the Clinician: The Tuesday Lessons. Goetz  CG, trans [with commentary].New York, NY: Raven Press; 1987.
5.
Charcot  J-M Lectures on the Diseases of the Nervous System. Sigerson  G, trans. London, England: New Sydenham Society; 1887.
6.
Charcot  J-M Lecture XII. Deuteropathic amyotrophies: lateral nervous system.  In:Lectures on the Diseases of the Nervous System.Sigerson  G, trans. London, England: New Sydenham Society; 1887:180-191.
7.
Charcot  J-M Lecture XIII. On amyotrophic lateral sclerosis. Symptomatology.  In:Lectures on the Diseases of the Nervous System.Sigerson  G, trans. London, England: New Sydenham Society; 1887:192-205.
8.
Charcot  J-M Charcot's disease: amyotrophic lateral sclerosis: a case of glossolabial laryngeal paralysis, February 28, 1888.  In:Charcot the Clinician: The Tuesday Lessons.Goetz  CG, trans [with commentary]. New York, NY: Raven Press; 1987;chap 8:164-186.
9.
Goetz  CG Amyotrophic lateral sclerosis: early contributions of Jean-Martin Charcot. Muscle Nerve.2000;23:336-343.
10.
Goetz  CGBonduelle  MGelfand  T Charcot. Constructing Neurology. Oxford, England: Oxford University Press; 1995.
11.
Aran  FA Recherches sur une maladie non encore décrite du systemé musculaire (atrophie musculaire progressive). Arch Gen Med.1850;14:5-35, 172-214.
12.
Duchenne de Boulogne  GB Recherches électro-physiologiques et thérapeutiques. Comp Rend Seances Acad Sci.1851;32:506.
13.
Cruveilhier  J Sur le paralysie musculaire, progressive, atrophique. Bull Acad Med.1853;18:490-501, 546-583.
14.
Gowers  W A Manual of Diseases of the Nervous System.  London, England: Churchill; 1886-1888.
15.
Brain  WR Diseases of the Nervous System.  London, England: Oxford University Press; 1933.
16.
Charcot  J-M Sclérose des cordons latéraux se la moelle épinière chez une femme hystérique atteinte de contracure permanente des quatre membres. Bull Memoires Soc Med Hop Par.1865:24-35.
17.
Charcot  J-MJoffroy  A Deuxcas d'atrophie musculaire progressive avec lésions de la substance grise et de faisceaux antérolatéraux de la moelle épinière. Arch Physiol Norm Pathol.1869;1:354-357; 2:628-649; 3:744-757.
18.
Eisen  AKrieger  C Amyotrophic lateral sclerosis. A Synthesis of Research and Clinical Practice.  Cambridge, England: Cambridge University Press; 1998:164-166.
History of Neurology
March 2001

How Amyotrophic Lateral Sclerosis Got Its NameThe Clinical-Pathologic Genius of Jean-Martin Charcot

Author Affiliations

From the Neurological Institute, Columbia-Presbyterian Medical Center, New York, NY.

 

CHRISTOPHER G.GOETZMD

Arch Neurol. 2001;58(3):512-515. doi:10.1001/archneur.58.3.512

Amyotrophic lateral sclerosis (ALS) occupies a unique place in the history of human disease in general and in neurological disease in particular. Charcot was the one who deduced the relationship between the clinical signs and the findings at autopsy. In his 1874 description,1 Charcot established the clinicopathologic approach that has dominated medical nosology ever since. In the latter half of the 19th century, diseases were defined by autopsy findings.

Charcot was the not first to describe cases of ALS. Tyler and Shefner2 credit Charles Bell with a report in 1824. Having distinguished the motor functions of anterior spinal nerve roots and the sensory functions of the posterior roots, Bell was interested in finding patients with purely motor disorders. Goldblatt3 also mentioned early cases.

By midcentury there were fiery debates among famous neurologists. Among the syndromes characterized by limb weakness and muscle atrophy, they ultimately came to separate neurogenic and myopathic diseases. It was not clear whether some syndromes were variants of the same condition or totally different disorders; this puzzle included progressive muscular atrophy, progressive bulbar palsy, primary lateral sclerosis, and ALS.

It was Charcot's achievement to make sense of the evidence linking "contracture" (deformity of limbs resulting from spasticity) to the corticospinal tract pathology, and linking the lower motor neuron signs to the loss of motor neurons. He was the first to use the term "amyotrophic lateral sclerosis."

Charcot's monumental contribution was made in a series of papers in French; historians favor the one that summarized his work.1 Fortunately for later generations, his thoughts were also recorded in English translations of the Tuesday Lectures at the Hôpital de la Salpêtrière4 and in translation by George Sigerson, who included the essential concepts of Charcot's ALS lectures in English.58 Goetz9 has brought the translations up-to-date.

However, the parallelism is not so clear. Sections I and II of Sigerson's Lecture XII (pages 180-185) correspond to pages 325-327 of Charcot's lectures,1 and Sigerson's pages 185 to 189 include pages 341 and 342 of Charcot. Sigerson's Lecture XIII (pages 199-204) incorporates pages 453 to 455 of Charcot. Sigerson did not give references to the journal article.

To comprehend the magnitude of Charcot's contribution we need to know the clinical state of affairs at the time, primarily 1850 to 1874. Goetz gave a clear picture in the masterly biography of Charcot he wrote with Bonduelle and Gelfand.10 Clinical diagnosis was rudimentary. The distinction between upper and lower motor neurons had not yet been made, and there was no understanding of the role of the corticospinal tract in connecting them. Among the concepts still lacking were the diagnostic value of overactive tendon reflexes, Hoffmann signs, and Babinski signs. At the lower end of the motor pathway, there was no way to separate different diseases manifest primarily by limb weakness. In 1850, Aran11 described cases and used the name "progressive spinal muscular atrophy" for these syndromes. But there had not been an autopsy study of those patients and there was no clinical distinction between neurogenic and myopathic diseases, a notion that was yet to come. An argument about priority ensued because Duchenne12 had studied all of Aran's patients with electrical stimulation, so he staked his claim. It is not clear whether Aran described Duchenne's patients, or vice versa. Duchenne's bid for priority12 was based on a notice of 50 words, not a scientific paper. The announcement stated that, at a weekly meeting of the Academy (French Academy of Science), he presented a collection of papers, which he called "Recherches Electro-Physiologiques," and which he intended to be used as evidence by future commission of authorities that never left a record, if it ever existed. The ultimate compromise was the eponym "Aran-Duchenne" syndrome.

But Cruveilhier, an unsung hero of this saga, made an essential contribution in 1853, when he described the pathology of ALS.13 He noted atrophy of the anterior roots and he suspected malfunction of the anterior horn cells. Charcot knew of that work and compared it with his own observations of anterior horn cell pathology in infantile spinal muscular atrophy, poliomyelitis, and other disorders characterized by muscular atrophy.

The terminology of these cases was not clarified for decades. Gowers is sometimes credited for introducing the term "motor neuron disease" in 1886-1888.14 However, that term must have come later because Gowers used only the terms chronic spinal muscular atrophy, ALS, or chronic poliomyelitis. Brain15 may have been the first to use "motor neuron disease"; in the first edition of his textbook, published in 1933, he gave "motor neuron disease" as a synonym for ALS (without mentioning why he used the new name).

On the other hand, Charcot also recognized that clinical signs of spasticity were associated with pathology in the lateral columns, as he recorded in his 1865 autopsy report on a woman whose limb contractures had been deemed "hysterical."16 That was an early example of primary lateral sclerosis.

He found, however, that these syndromes were not always limited to one or the other set of findings; some patients showed both amyotrophy and spastic contractures. Charcot was therefore ready to combine both sets of observations, which he did with Joffroy 1869.17 They described "two cases of progressive spinal muscular atrophy with lesions of the gray matter and anterolateral fascicles of the spinal cord." In that paper, they set down concepts and observations that now seem familiar and fundamental:

We encountered several patients with the following conditions: paralysis with spasms of the arms and principally the legs (without any loss of sensation), together with progressive amyotrophy, which was confined mostly to the upper limbs and trunk.17(p747)

"In this woman (the reported case of Dumenil), the tongue did not appear noticeably smaller but it was constantly agitated in small jerky movements and a kind of fibrillary trembling. The surface of the tongue was uneven, with rough and puckered areas. At autopsy a large number of atrophied nerve fibers were found in the roots of the hypoglossal nerve as well as in the anterior roots of the spinal nerves.17(p747)

In the gray substance we found only a small number of well developed cells, one or two in each sample, side by side with deformed and atrophied cells that were deprived of their extensions.17(p747)

. . . symptoms of progressive muscular atrophy developed in succession. In the final stages of the illness, symptoms of paralysis and spasticity developed, which seem to have been linked to the symmetrical sclerosis. . . . Thereafter, the irritation centered in the dura mater and the pia mater will spread farther . . . advancing all the way to the gray matter. At the same time, the symptoms of amyotrophy appear.17(p746)

By this time, Charcot had clearly linked clinical amyotrophy to autopsy pathology of the anterior horn cells or motor neurons of the cranial nerves. "Amyotrophy" was then a synonym for muscular atrophy. He had also discerned the origin of spastic paraparesis in disease of the lateral columns. But at least one of the early patients may have had chronic meningitis and he therefore sought to study cases of what he called "protopathic" (primary amyotrophy, not secondary to some other process) to clarify the problem. However, this approach was entirely not clear because he considered ALS to be "deuteropathic," assuming that the motor neurons degenerated because of a failure of descending fibers in the lateral columns. Nevertheless, Charcot did accumulate cases in which no other cause for the disorder was apparent.

It was another 5 years before he reviewed this new experience and first used the term "amyotrophic lateral sclerosis," which appeared in the title of the paper.1 In part IV of that series, he recorded more observations that have become standard teachings:

Amyotrophic paralysis starts in the upper limbs as a cervical paraplegia. After 4, 5, 6 months or more, the emaciation spreads and there is protopathic muscular atrophy, which advances for 2 or 3 years. After a delay of 6 or 9 months, the legs are affected . . . but the muscles are conserved and contrast singularly with the state of the upper limbs.

There is no paralysis of the bladder.

The patient has more difficulty walking and then cannot stand . . . After some time, the patient has noticed that, in bed or sitting, the legs sometimes extend or flex until a position is produced involuntarily . . . and the legs come to resemble a rigid bar. The rigidity is exaggerated when the patient is held up by assistants who want to walk him. The feet take on a posture of equinus varus. This rigidity, often extreme, affects all joints by a spasmodic action of the muscle. The tremor interferes with standing and walking.

If one flexes the extended foot, one can evoke a tremor, more or less persistent. The motor disorder (in the legs) owes less to weakness than to a spastic state of the muscle. The muscles are also in a state of fibrillary movement and become atrophic as a group, for example, in the arms. The failure of motor function is less connected to weakness than to the spastic condition of the muscles. It is only in the long run that one sees the leg muscles seized by fibrillary movement and to become completely atrophic as in the upper limbs. In general, when the atrophy reaches a certain degree, the rigidity decreases without ever actually disappearing.

The appearance of the last symptoms is in some ways obligatory but not always present. Taken together these phenomena compose the syndrome called labio-glosso-laryngeal paralysis.

The following are the symptoms: 1) Paralysis of the tongue following difficulty swallowing and pronouncing words, which can progress to complete loss of speech. Soon, the paralyzed tongue shows atrophy; it is furrowed with ridges and agitated with vermicular movements. 2) Paralysis of the uvula, which makes speech nasal and, in combination with laryngeal paralysis, leads to dysphagia. 3) Paralysis of the orbicularis of the lips, which distorts the appearance of the face. The mouth is enlarged transversely to a great degree, followed by twitching of the facial muscles thus far unaffected. The nasolabial folds are accentuated. These symptoms alter the physiognomy to give an appearance of weeping. The mouth remains partly open permanently and is constantly drooling viscous saliva. 4) Finally, the vagus nerve is affected with grave difficulty breathing and of the circulation, leading to death of a person already so weakened by insufficient nourishment.

I will now try to summarize the features of amyotrophic lateral sclerosis:

1) Paralysis without loss of sensation of the upper limbs, accompanied by rapid emaciation of the muscles . . . At a certain time, spasmodic rigidity always takes over with the paralyzed and atrophic muscles, resulting in permanent deformation by contracture.

2) The legs are affected in turn. Shortly, standing and walking are impossible. Spasms of rigidity are first intermittent, then permanent and complicated at times by tonic spinal epilepsy. The muscles of the paralyzed limb do not atrophy to the same degree as the arms and hands. The bladder and rectum are not affected. There is no tendency to the formation of bedsores.

3) In the third period, the preceding symptoms worsen and bulbar symptoms appear. These three phases happen in rapid succession—6 months to a year after the onset, all the symptoms have appeared and become worse. Death follows in 2 or 3 years, on average, from the onset of bulbar symptoms. This is the rule but there are a few anomalies. Symptoms may start in the legs or be limited to one side of the body, a form of hemiplegia. In two cases, it started with bulbar symptoms.

At present, the prognosis is grave. As far I know, there is no case in which all the symptoms occurred and a cure followed. Is this an absolute block? Only the future will tell.

Doubtless, the weakness and permanent contractures that follow rapidly depend on the lateral and symmetrical sclerosis.

Let me remind you that wherever we encounter lateral sclerosis, contracture appears sooner or later, as in: a) multiple sclerosis; b) cerebral hemiplegia with descending sclerosis; c) transverse myelitis following compression or as a spontaneous disorder with descending lateral degeneration; and d) primary sclerosis of the lateral columns without muscular atrophy.

Charcot therefore gave a complete picture of ALS, emphasizing lower motor neuron signs in the arms and upper motor neuron signs in the legs. His description of the natural history, lamentably, has not changed much in 126 years. He described the bulbar syndrome in detail. He described clonus and he may have been the first to use the term "primary lateral sclerosis."

He thought the anterior horn pathology followed and was caused by disease of the lateral columns. He drew a parallel with anterior horn cell pathology in multiple sclerosis, a concept not now in favor. The general consensus is that both upper and lower motor neurons are affected independently but usually simultaneously in ALS. Eisen and Krieger,18 however, have adduced physiologic evidence that reinforced Charcot's ideas about the significance of upper and lower motor neuron pathology.

By proving that upper motor neuron signs implicate the corticospinal tracts and amyotrophy, the anterior horn cells, Charcot established the clinicopathologic method for defining disease and led the way to the modern neurological examination. More than a century later, we still define and diagnose ALS by clinical criteria and prove it by autopsy.

Amyotrophic lateral sclerosis was not the end of the story. Charcot returned to study Aran's patients who had forms of muscular atrophy that did not prove to be ALS. Among them, he found a new class of disease with his famous student Pierre Marie; thus came Charcot-Marie-Tooth disease. (Tooth, an English neurologist, made his independent observations in the same year.)

Charcot was surely a clinical genius, but his premier paper might not fare so well had he submitted it to a modern editorial board. The text is much too long. Also, sample size could have been a problem. According to Goetz, Charcot based his conclusions on only 5 patients he had examined personally; these were augmented by 15 other cases. Entry criteria were not clearly stated, and the pathologist knew the clinical details of the patient whose tissues he examined. Charcot published the names and initials of patients, violating a canon of current sensitivity about the invasion of privacy.

Fortunately, we do not have to be concerned about modern editors. Charcot published his lasting observations in 1874. His own assessment was clearly stated:

I do not think that elsewhere in medicine, in pulmonary or cardiac pathology, greater precision can be achieved. The diagnosis as well as the anatomy and physiology of the condition "amyotrophic lateral sclerosis" is one of the most completely understood conditions in the realm of clinical neurology.

Accepted for publication June 12, 2000.

The author has depended on the earlier reviews of others, especially the elegant and comprehensive writings of Christopher Goetz, MD. For assistance in translation, he was greatly aided by Esther Rowland, BA, MA, Helen Solterer, PhD (Duke University, Durham, NC), and Jean Pouget, MD (Université Aix, Marseilles, France). Edward Morman, MLS, PhD, Associate Director for Historical Collections, The New York Academy of Medicine Library, found a legible copy of all 4 sections of Charcot's landmark paper of 1874 (reference 1). Dr Morman recognized a third section (pages 421-423), which had been omitted from an earlier reference. Some translations of the lectures are taken from the collected works of Charcot, rather than the journal article we used. Caroline Duroselle-Melish, MA, MLS, the rare book room reference librarian at the Academy also participated in the searches. Elizabeth La Rue, MLS, Columbia Health Services Library, helped throughout the process.

Corresponding author: Lewis P. Rowland, MD, Neurological Institute, 710 West 168th St, Columbia-Presbyterian Medical Center, New York, NY 10032 (e-mail: lpr1@columbia.edu).

References
1.
Charcot  J-M De la sclérose latérale amyotrophique. Prog Med.1874;2:325-327, 341-342, 453-455.
2.
Tyler  HRShefner  J Amyotrophic lateral sclerosis. Handb Clin Neurol.1991;15:169-215.
3.
Goldblatt  D Motor neuron disease: historical introduction.  In: Norris  FH Jr, Kurland  LT, eds.Motor Neuron Disease. New York, NY: Grune & Stratton; 1968:3-11.
4.
Charcot  J-M Charcot the Clinician: The Tuesday Lessons. Goetz  CG, trans [with commentary].New York, NY: Raven Press; 1987.
5.
Charcot  J-M Lectures on the Diseases of the Nervous System. Sigerson  G, trans. London, England: New Sydenham Society; 1887.
6.
Charcot  J-M Lecture XII. Deuteropathic amyotrophies: lateral nervous system.  In:Lectures on the Diseases of the Nervous System.Sigerson  G, trans. London, England: New Sydenham Society; 1887:180-191.
7.
Charcot  J-M Lecture XIII. On amyotrophic lateral sclerosis. Symptomatology.  In:Lectures on the Diseases of the Nervous System.Sigerson  G, trans. London, England: New Sydenham Society; 1887:192-205.
8.
Charcot  J-M Charcot's disease: amyotrophic lateral sclerosis: a case of glossolabial laryngeal paralysis, February 28, 1888.  In:Charcot the Clinician: The Tuesday Lessons.Goetz  CG, trans [with commentary]. New York, NY: Raven Press; 1987;chap 8:164-186.
9.
Goetz  CG Amyotrophic lateral sclerosis: early contributions of Jean-Martin Charcot. Muscle Nerve.2000;23:336-343.
10.
Goetz  CGBonduelle  MGelfand  T Charcot. Constructing Neurology. Oxford, England: Oxford University Press; 1995.
11.
Aran  FA Recherches sur une maladie non encore décrite du systemé musculaire (atrophie musculaire progressive). Arch Gen Med.1850;14:5-35, 172-214.
12.
Duchenne de Boulogne  GB Recherches électro-physiologiques et thérapeutiques. Comp Rend Seances Acad Sci.1851;32:506.
13.
Cruveilhier  J Sur le paralysie musculaire, progressive, atrophique. Bull Acad Med.1853;18:490-501, 546-583.
14.
Gowers  W A Manual of Diseases of the Nervous System.  London, England: Churchill; 1886-1888.
15.
Brain  WR Diseases of the Nervous System.  London, England: Oxford University Press; 1933.
16.
Charcot  J-M Sclérose des cordons latéraux se la moelle épinière chez une femme hystérique atteinte de contracure permanente des quatre membres. Bull Memoires Soc Med Hop Par.1865:24-35.
17.
Charcot  J-MJoffroy  A Deuxcas d'atrophie musculaire progressive avec lésions de la substance grise et de faisceaux antérolatéraux de la moelle épinière. Arch Physiol Norm Pathol.1869;1:354-357; 2:628-649; 3:744-757.
18.
Eisen  AKrieger  C Amyotrophic lateral sclerosis. A Synthesis of Research and Clinical Practice.  Cambridge, England: Cambridge University Press; 1998:164-166.
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