What are the symptoms, progression and life expectancy of Charcot disease?

While progressive paralysis of all the muscles is the main feature of Charcot's disease, its course can vary greatly from patient to patient.
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The symptoms of amyotrophic lateral sclerosis (ALS) or Charcot’s disease are characterised by complete paralysis of the muscles of the arms, legs and throat, leading to a progressive inability to walk, eat, speak or even breathe. Amyotrophic lateral sclerosis (ALS) begins in adulthood (40-80 years) and progresses, in 3 to 5 years, to complete paralysis and death, generally due to paralysis of the breathing muscles.

The initial symptoms of Charcot disease vary depending on the location of the motor neurons affected at the onset of the disease:

  • In most cases, the disease begins with motor weakness of the upper or lower limbs, known as the spinal form of the disease. The affected limbs may atrophy and become flaccid when the peripheral motor neuron is most affected, or become stiff when the central motor neuron is most affected. Most often, patients experience cramps and fasciculations (small, brief, diffuse muscle contractions that do not result in joint movement). Muscle weakness begins locally, then worsens and gradually spreads to other areas of the body.
  • In around 30% of cases, Charcot’s disease begins with damage to the motor neurons in the brain stem (bulbar form) and the first sign is difficulty in articulating. Difficulty swallowing, in the form of false routes, is most often rapidly associated. In this form of the disease, there is also an excess of saliva in the mouth and hyperemotionality.
  • In rarer cases (around 10%), the disease may begin with damage to the musculature of the trunk, resulting in a “drooping” head and difficulty in keeping the trunk upright when walking and/or an impairment of inaugural breathing.
  • In most cases, the disease that begins in one region of the body spreads to the others, so that patients with a spinal form may subsequently develop bulbar symptoms, or vice versa.
  • All patients will develop damage to their respiratory muscles, leading to respiratory failure in the most advanced stages. It is this respiratory failure that can be life-threatening, leading to death.

At the Paris Brain Institute

Deciphering the role of immunity in Charcot disease

Séverine BOILLEE is studying the influence of immune cells (or inflammation cells) on motor neuron degeneration and disease progression. In ALS, inflammation cells are much more present around the motor neuron than in non-diseased subjects. They react to the degeneration of the motor neurons and are involved in the progression of Charcot’s disease. In the brain and spinal cord, motor neurons interact with microglial cells, while in the peripheral nervous system they are in contact with macrophages. These two types of cell play a dual role: positive, by sending factors that are beneficial to the survival of motor neurons, and negative, via toxic factors that contribute to their destruction. Séverine BOILLEE and Christian LOBSIGER’s research aims to gain a better understanding of the role of these cells in the development and progression of Charcot’s disease, in order to identify new therapeutic avenues. The aim is to analyse precisely the different factors emitted by these cells in order to identify those on which action can be taken to slow the progression of the disease.

Early cerebral changes in individuals at risk of developing ALS

A study promoted by the AP-HP and conducted at the Institut du Cerveau at the Hôpital de la Pitié-Salpêtrière by Isabelle LE BER in the team led by Alexandra DURR and Giovanni STEVANIN and Olivier COLLIOT co-leading the team with Stanley DURRLEMAN has shown, for the first time, that asymptomatic individuals at risk of developing frontotemporal degeneration (FTD) or Amyotrophic Lateral Sclerosis (ALS), because they carry the C9ORF72 gene mutation, show very early cognitive, anatomical and structural changes, before the age of 40. The identification of biomarkers at very early stages is a first step towards developing the tools needed to evaluate new treatments. The development of therapies at an early stage, ideally before the onset of symptoms, requires the development of tools that can tell us when to initiate treatment and measure its effectiveness.