Website Edition: August/September 2009

Jean-Martin Charcot and Movement Disorders: Neurological Legacies to the 21st Century

Christopher G. Goetz, MD

Movement Disorder Society 2009 Presidential Award: Stanley Fahn Lecture in Clinical Research

Jean-Martin Charcot was the premier clinical neurologist of the 19th century. He spent his entire career at the Salpêtrière hospital in Paris and raised the institution from a hospice for old women into a Mecca of neurological study. His lectures drew students and colleagues from around the world and trained a generation of younger neurologists who would largely dominate the neurological world in the generation after his death. His service was organized as a very tight and authoritatively managed unit with a core team, termed the circle intime or inner circle. Around this halo, there was a large array of visitors and students. Many of his long-standing contributions focused on movement disorders, with lessons that still apply to neuroscientists of the 21st century.

The anchor of C's research technique was the anatomo-clinical method or the méthode anamo-clinique. With this term, adapted from the methods of Laennec, Charcot placed dual emphasis on clinical or hospital medicine and laboratory science, emphasizing the resultant cross fertilization: In his own words:

I firmly believe that in medicine there are areas that belong solely to doctors for only they can properly cultivate and bring these areas to fruition. These domains are necessarily closed to scientists who day in and day out are confined to their laboratory and would disdain the teaching methods of the hospital.. But I believe with equal fervor that the anatomy and physiology laboratories must have input into the issues of medical science in order for medicine to progress. To me, the practice of medicine has no real autonomy: it exists by borrowing and making new application of ideas from other disciplines. Without a constant reinfusion from other scientific domains, the practice of medicine would soon become an outmoded routine.

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Figure 1: Patient record from the Bibliothèque Charcot, Paris, France

This two part strategy of the AC method involved first thorough and unbiased documentation of clinical signs and second the autopsy findings. In the first phase, the examination of large series of patients with similar or contrasting signs was facilitated because the Salpêtrière housed over 5,000 chronically ill and life long residents of the institution. As wards of the state, the second phase was feasible because these patients were automatically available for autopsy study at death. The correlation between clinical signs and anatomical lesions was the core axis of Charcot neurological methodology. In the archives of the Bibliothèque Charcot, Paris, his original patient files document the accumulated patient records, ancillary supportive materials and autopsy material (Figure 1).

In his early years as a staff physician and with some help from his colleague Vulpian, Charcot categorized patients from the masses of randomly agglomerated patients as shown here into units based on their predominant neurological signs, weakness, tremor, convulsions and others. Within each category, he studied prototypic cases and subdivided each class into further designations. As such, he provided the first sound nosography in neurology. As an example, specific to movement disorders, among tremor patients, heretofore assembled together, Charcot examined tremor relationship to rest and to activity. He noted that some patients had tremor only during activity whereas others had exclusively rest tremor. As he would find with the second step of the AC method, these different clinical groups would also be fundamentally different in terms of neurological lesions. Those with action tremor would have the disseminated white matter lesions of what his older colleague Cruveillhier had already defined pathologically as multiple sclerosis after death. The rest tremor patients had slowness, rigidity and balance problems and would be classified as having Parkinson's disease, a névrose or neurological disorders without a definitive lesion. Charcot's students discovered the brain stem lesions of our cherished disorder after their mentor's death.

The clinical phase of the AC method was highly detailed and creative scientifically. To depict the Parkinson's disease patients, he engaged medical artists and medical sculptors to capture static signs of archetypal cases. He also made plaster and wax casts of deformities. These materials were used in teaching sessions, publications and also transported to international meetings to great international acclaim. For gait analysis, he had patients step into ink pads or cinder boxes and walk on a surface to document their gait patterns. Charcot adapted tools from other fields and added to the field of medical illustration a wing to embrace the new field of photography. Following this evolving field with avid interest, he incorporated multiframe timed photography to capture mobile disorders like this patient with Gilles de la Tourette syndrome. In all aspects of this first phase of the anatomo-clinical method, Charcot was a visual scientist, relying most heavily on unbiased observation. Current movement disorder specialists, likewise, anchor their efforts in a reliance on their discriminative visual sense. Charcot reminded his students in his lecture on Feb 28, 1888:

Let someone say of a doctor that he really knows his physiology or anatomy, that he is dynamic-these are not real compliments, but if you say that he is an observer, a person who knows how to see, this is perhaps the greatest compliment one can make.

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Figure 2: Parkinson's disease patient sketched by Charcot

The second step of his AC method was to conduct a systematic autopsy of patients and to correlate signs with specific lesions. Charcot's separation of Parkinson's disease from multiple sclerosis was the first fruit of this strategy based on combined clinical-pathological correlations.

Charcot never lost the opportunity to document neurological disorders regardless of work or family vacation. While visiting Morocco, at that time part of France, he sketched a parkinsonian subject (Figure 2). Though not a skilled artist, his sketches captured the essential qualities, here the joint deformities, rigid posture and the shadowing evokes tremor. Charcot was impressed by the tremor and rigidity of PD, but most interested in the slowness of movement. Charcot's recognition of bradykinesia, never mentioned by P himself, remains a seminal document: He said to his students:

Long before rig actually develops, patients have significant difficulty performing ordinary activities; this problem relates to another cause. In some of the various pts I showed you, you can easily recognize how difficult it is for them to do things even though rigidity or tremor is not the limiting features. Instead, even a cursory exam demonstrates that their problem relates more to slowness in execution of movement rather than to real weakness. In spite of tremor, a pt is still able to do most things, but he performs them with remarkable slowness. Between the thought and the action there is a considerable time lapse. One would think neural activity can only be effected after remarkable effort.

He also appreciated the posture and gait difficulty of PD and drew this typical patient. He lectured:

If you tap on this patient, he will propulse forward and his gait will be quite unusual. His head bends forward, he takes a few steps and they become quicker and quicker to the point that he can even bump into the wall and hurt himself. If I pull on his trousers from behind, he will retropulse in the same distinctive way.

The volume of patients, as shown in these drawings of the S population, allowed Charcot the opportunity to continually reinforce and modify his thinking. Having established the prototypic phenotype of PD, he moved further to assess the variants of the archetype. His lesson from the 19th century still resonates for those of us who must deal with problematic cases and differential diagnoses. He stated:

Studying archetypes is the fundamental task in nosography. It is indispensable and the only way to extract from the chaos of imprecision a specific pathological state. But once the archetype is established, the second operation begins: dissect the archetype and analyze its parts. One must in other words learn how to recognize the imperfect cases, the formes frustes or examples where only one feature occurs in isolation. I stress that by using this second method, the physician will see the archetypical illness in an entirely new light. One's scope enlarges and the illness becomes much more important to the doctor's daily practice. To the patient's benefit, the doctor becomes attentive and sensitive to recognizing a disease even when it is in its earliest developmental stages.

Charcot drew the distinction between the typical Parkinson's disease and parkinsonian cases with extended postures and no tremor. Such cases (Figure 3) likely would be classified as progressive supranuclear palsy in contemporary nosology.

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Figure 3: Differences between a typical patient with Parkinson's disease (flexed posture) and an atypical case with extended posture, no tremor, and contractions of the frontalis muscle, a case likely to be classified today as progressive supranuclear palsy

Charcot was never daunted by complicated cases that did not quite fit his archetypal picture. Charcot warned his students:

Because the patient is so complex, he is a real study subject. After all, clinical medicine is above all the study of the difficult aspects and complexities of diseases. When a pt calls on you, he is under no obligation to have a simple disease just to please you.

Whereas Charcot had great vision in terms of incorporating modern technology and international advances into a synthesized view of neurological illness, he was nonetheless a man of his times. Very little focus was ever placed on causation of illness, and infectious, metabolic, and environmental etiologies were not seriously considered. In the 19th century, the primary assumption was that neurological disorders were hereditary and this perspective was both an advantage and disadvantage to Charcot. He lectured frequently on the concept that families carried a neurological trait or tache that weakened their neurological system and placed them at risk for disease. The actual phenotype within a family however could vary and this neurological trait could manifest as chorea, aphasia, ataxia or any neurological syndrome in various family members. Rarely, as in Huntington's disease, the pattern followed what he called "similar transmission" where the phenotype remained static from generation to generation. In his view, however, this pattern of similar transmission was not fundamentally different than the more typical cases where manifestations varied. His lectures on Huntington's disease were pivotal to the wide acceptance of the disease that had been described in an obscure medical journal by an otherwise obscure country physician in the United States. He failed, however, to distinguish Sydenham's chorea from Huntington's disease, because of his assumption that SC like any other neurological illness was likewise hereditary. In accepting family trees with different neurological manifestations of a single presumed hereditary etiology, Charcot would be bolstered by several 21st century observations. Spinocerebellar atrophies today are known to have a wide phenotypic variability but a single gene defect, and, in the search for the gene for Gilles de la Tourette syndrome, researchers continue to wrestle with the the genetic implications of cases of hyperactivity without tics and obsessive-compulsive disorder within the families of tic subjects.

As a person, Charcot was a quiet, authoritative and stocky man, described as Napoleonic or liken to the Roman Caesars. Teaching was formalized and hierarchical as shown in the sketch from his daily rounds. In the hospital, he was distant, often cold, but his power and devotion to his students earned him a strong fidelity among his junior staff. They were invited to his evening soirées and mingled with political figures, European royalty, some who were his own patients. Through Charcot's celebrity, his inner circle of devotees were exposed to artistic and theatrical figures of the day. In the winter season, the family lived on the Blvd St. Germain in a mansion that can still be visited with its internal garden. In the summer, the family retreated to their chalet in the Bois de Boulogne. This later house sits besides high rise apartment houses today, but remains in the Charcot family home and is a national landmark that can be visited by contacting Charcot's descendants (Figure 4).

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Figure 4: Charcot's homes
Hôtel de Varangeville, 217, boulevard St Germain, Paris
(left)
29, rue St James, Neuilly-sur-Seine (right)

Movement disorders is a neurological area that abounds in treatment opportunities, and Charcot was alert to early remedies. Through his supervision of his intern's Ordenstein's thesis, he identified anticholinergic drugs as beneficial in parkinsonian tremor. He also used rye-based compounds, and clinicians will appreciate that the early dopamine agonists were all ergot-based.

Charcot emphasized the importance of searching for new therapies. With his attention to the international literature, he learned of a suspension therapy advocated in Russia and set up this apparatus for trials at the S. He documented the lack of improvement and abandoned it quickly. Based on observations that patients with PD felt relief from pain and fatigue after a carriage or train ride, C developed this vibratory chair and tested it in patients. He found that sessions of 30 minutes multiple times weekly improved symptoms and sleep. Vibration therapy has emerged as a therapy in sports medicine, orthopedics and some areas of neurology. Modern equipment is available for total body vibration, and some of these observations from the very end of Charcot's career may merit testing again in a modern context.

In all his therapeutic efforts, Charcot was adamant that the physician should not place his patient at risk, a lesson that resonates today, over 100 years after his death: He stated and I quote: if you do not have a proven treatment for certain illnesses, bid your time, do what you can, but do not harm your patients.

I wish to close with a reflection by Charcot as he faced the challenges of dealing with incurable diseases, a situation that modern movement disorder specialists face daily. The case presentation involved a man with incurable disease, and after comforting the patient and allowing him to exit the lecture hall, he turned to his students with these words:

Now, that the patient is no longer here, we can and must speak amongst ourselves in total frankness. The most varied remedies with the most logical bases will be entirely impotent to slow the progressive advance of this disease. It is sad to say, but it is true. However, for the doctor, whether it is sad or not is not the issue: truth is the issue. Let us keep looking in spite of everything. Let us keep searching for it is indeed the best method for finding. And perhaps, thanks to our efforts, the verdict we will give such a patient tomorrow will not be the same as we must give him today.