Charcot disease: diagnosis could be simpler thanks to electroencephalography

New discoveries on Charcot disease have just been brought to light by French researchers.

Charcot disease: a difficult diagnosis to establish

There “amyotrophic lateral sclerosis (ALS)”, Or “Charcot’s disease”, is a neurodegenerative pathology which leads to progressive paralysis and then the death of the patient in just two to five years. It is caused by the death of motor neurons, the nerve cells that control muscles in the brain and spinal cord.

No curative treatment exists to date, and the diagnosis of ALS is still difficult to make. “Indeed, the manifestations of Charcot disease are heterogeneous at the start of the disease: weakness or cramps in an arm, a leg, swallowing or articulation difficulties…”, explains Inserm. “Furthermore, there is no specific biomarker for the disease. Thus, the diagnosis results from the elimination of other pathologies that could cause motor disorders, which generally takes one to two years after the onset of symptoms, delays the implementation of therapeutic measures and reduces the chances of inclusion in early-stage clinical trials”, adds the research center.

Charcot disease: what is the contribution ofelectroencephalography?

It is therefore with the objective of shortening the diagnosis time that the teams of Caroline Rouaux (Strasbourg Biomedicine Research Center), Sabine Liebscher (Institute of clinical neuroimmunology

) and Véronique Marchand-Pauvert (Inserm), tested the use of electroencephalography. This easy-to-use technique involves placing electrodes on the surface of the skull to record brain activity in the form of waves.

Several examinations carried out in subjects suffering from ALS and on animals suffering from the same disease have revealed an imbalance between two types of waves respectively associated with the activity of excitatory and inhibitory neurons, which reflects cortical hyperexcitability. This phenomenon was found in all subjects tested and increases when the symptoms of Charcot disease progress.

“This singularity is not a surprise and had already been described with other investigation methods, but these are very little used because they are difficult to implement and only work at the very beginning of the disease” , explains Caroline Rouaux. “Electroencephalography, on the contrary, is minimally invasive, very inexpensive, and can be used at different times during the disease. Furthermore, the atypical brain wave pattern revealed by electroencephalography could prove to be specific for the disease. she continues.

“Opening of a new therapeutic avenue for Charcot disease”

In a second part of their work, the researchers were able to study the mechanisms behind the hyperexcitability observed previously in patients and sick mice. On this occasion, they found that norepinephrine* was present in lower quantities in the brains of patients and rodents suffering from Charcot disease compared to healthy brains.

To verify the role of norepinephrine, they blocked the production of this neuromodulator in healthy animals, and thus showed that this causes cortical hyperexcitability like that observed in amyotrophic lateral sclerosis. Conversely, by administering molecules stimulating the action of norepinephrine in mice with ALS, scientists reduced hyperexcitability and restored brain activity equivalent to that of healthy mice.

“This discovery could mark the opening of a new therapeutic avenue in ALS provided that cortical hyperexcitability is indeed associated with the progression of the disease. Indeed, to date, we have observed in our study an association between two but no cause and effect link has yet been established. This is what we will verify in the coming months”, concludes Caroline Rouaux.`

*Norepinephrine is the neurotransmitter of the sympathetic nervous system.