Charcot disease: a study shortens diagnosis and improves patient monitoring

Charcot disease: a study shortens diagnosis and improves patient monitoring

Charcot disease affects 1000 new people each year in Europe. Its diagnosis often takes a long time, one to two years after the onset of symptoms, but a new study could greatly reduce this delay and even offer new avenues for treatment.

A diagnosis that takes one to two years

Amyotrophic lateral sclerosis or Charcot disease most often occurs between the ages of 50 and 70. It leads to progressive paralysis, due to the death of motor neurons, the nerve cells that control muscles, both in the brain (central motor neurons) and in the spinal cord (peripheral motor neurons).

Today, the diagnosis of ALS is not easy: there is no biomarker for the disease and the first symptoms are heterogeneous: weakness or cramps in an arm or a leg, difficulty swallowing. or joint… It is therefore by eliminating other pathologies that the diagnosis is made, which generally takes one to two years after the onset of symptoms and delays the implementation of therapeutic measures and reduces the chances of inclusion in early-stage clinical trials.

Towards faster diagnosis and simpler prognosis

To shorten this time, a Franco-German team tested the use of electroencephalography, an inexpensive and easy-to-use technique consisting of placing electrodes on the surface of the skull to record brain activity in the form of waves.

The examination carried out in subjects with ALS and in models revealed an imbalance between two types of waves “theta” and “gamma” respectively associated with the activity of excitatory and inhibitory neurons. This imbalance, in favor of greater activity of excitatory neurons to the detriment of inhibitory neurons, reflects cortical hyperexcitability. “This phenomenon is not a surprise and had already been described with other investigation methods, but these are rarely used because they are difficult to implement and only work at the very beginning of the disease. 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“, explains Caroline Rouaux, Inserm researcher and final author of the study.

Not only was this imbalance found in all the subjects tested, but the scientists also showed that the more the symptoms of the disease progress, the greater this imbalance. This atypical wave profile was even detected in animals before the appearance of motor symptoms.

If these results are confirmed, electroencephalography could serve as a diagnostic but also prognostic tool for diagnosed patients in order to evaluate, for example, the response to treatment.

Towards a new therapeutic avenue?

The researchers also studied the mechanisms behind the observed hyperexcitability in patients and mice. They found a norepinephrine deficiency in the brains of ALS patients and mice, compared to healthy brains. By blocking the production of this neuromodulator in healthy animals, they showed that this causes cortical hyperexcitability, like that observed in the disease. Conversely, by administering molecules stimulating the action of norepinephrine in a mouse model of 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 observe in our study an association between the two but no cause and effect link has yet been established. This is what we will check in the coming months“, concludes Caroline Rouaux.