What is Charcot marie tooth disease?

Jean-Martin Charcot, answered from the texts and cited to the page.

Jean-Martin Charcot answers

The affection you name was not yet called by that name in my own clinical work, but the disease itself — I can speak to it precisely, for the cases were before me and my colleagues at the very moment the nosographical boundaries were being drawn. What you refer to is the progressive muscular atrophy arising from lesion of the peripheral nerves rather than of the spinal cord — the form Pierre Marie and Howard Henry Tooth described shortly after my own lectures had laid the groundwork for distinguishing precisely these varieties.

The clinical picture is characteristic: atrophy beginning in the lower extremities, the legs wasted while the thighs remain comparatively spared, and a gait of that peculiar high-stepping quality produced by weakness of the muscles governing dorsal flexion of the foot.¹ The patient, in raising the leg to carry it forward, cannot prevent the foot from dropping, and so must flex the knee to an exaggerated degree — an imitation, one might say, of the high-stepping horse.¹

This I had occasion to demonstrate in the case of the young woman Dali —, twenty-four years of age, whose disease had commenced at fourteen in the lower extremities and spread to the upper at twenty.² The deeper nosographical question — whether such cases belong to a spinal atrophy of the Duchenne-Aran type, or represent something distinct — occupied me considerably.

My position was that these cases of atrophy commencing in the legs, often with hereditary transmission running through families across several generations, were separable from the great Duchenne-Aran group and belonged rather among the primary progressive myopathies, or — as the peripheral nerve hypothesis gained ground — to a category of their own.³⁴

The anatomical difficulty was real. I noted that for generalised amyotrophy arising purely from peripheral nerve lesion, well-verified anatomical demonstration was, at the moment of my lectures, still wanting — the chapter, as I put it, somewhat resembled a frame without a picture.⁵ The cases communicated to me by Joffroy and Pierret, in which a generalised atrophy seemed connected with peripheral nerve lesion while the spinal cord remained healthy, pointed in the right direction, and the affection Grainger Stewart described — sensory disorders first, then paresis spreading distally from the fingers and toes upward, with rapid muscular atrophy and loss of the knee-jerk — represents the clinical territory in which Charcot-Marie-Tooth disease sits.⁶⁷

What the eponym now fixes is a hereditary peripheral neuropathy: the lesion is in the nerve, the atrophy is secondary to it, the distribution is distal and ascending, and the hereditary element — traceable, in some families, across five generations — is among its most constant characters.³ That the disease is real, that it is distinct from spinal progressive atrophy, and that its seat is in the peripheral nerve rather than the anterior cornua of the cord — this the anatomo-clinical method was already moving toward when my pupils and Tooth completed the demonstration.

Sources

1. as a consequence of the feebleness of the muscles of the leg, the point of the foot falls when the patient, in walking, raises the leg so as to carry it forward… she is obliged to flex the knee to an unnecessary extent so as not to allow the point of the foot to trail on the ground, imitating the movements of a high-stepping horse.

   Lectures on Diseases of the Nervous System, Series III

2. The disease commenced at the age of fourteen, in the lower extremities; then the upper extremities were attacked in their turn at the age of twenty.

   Lectures on Diseases of the Nervous System, Series III

3. H. Naunyn, Professor at Konigsberg, narrated the history of a family in which the transmission of the disease could be traced through five generations.

   Lectures on Diseases of the Nervous System, Series II

4. it is highly probable that, like this, it can be classed amongst the primary progressive myopathies of non-spinal origin.

   Lectures on Diseases of the Nervous System, Series III

5. this chapter of nosography seems to me somewhat to resemble a frame without a picture. There does not, in reality, exist, to my knowledge, at least, a single published observation in which anatomical demonstration has been given of this neuritis, or this progressive nerve atrophy.

   Lectures on Diseases of the Nervous System, Series II

6. M. Joffroy and M. Pierret have each recently communicated to me a case in which a generalised atrophy, rather ill characterised clinically, would seem to be connected with lesion of the peripheral nerves. The spinal cord was quite healthy in both cases.

   Lectures on Diseases of the Nervous System, Series II

7. Sensory disorders, such as pain or, more commonly, numbness and tingling, are the first to appear… Paresis affecting the distal parts speedily ensues, spreading up the limb from one group of muscles to another… Trophic changes, such as rapid muscular atrophy… are apt to make their appearance. The knee-jerk disappears early.

   Lectures on Localisation of Cerebral and Spinal Diseases