Creutzfeldt-Jakob disease is a rare neurodegenerative pathology, from the family of prion diseases, which is manifested in particular by dementia. It can be “sporadic”, hereditary or “acquired” (iatrogenic, mad cow disease). Causes, symptoms, transmission, treatment with Dr. Jean-Philippe Brandel, neurologist.
Definition: what is Creutzfeldt-Jakob disease?
The Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disease who touch the man and is mainly characterized by dementia with neurological signs the most common of which are myoclonus (irregular muscle twitches) and balance problems. It belongs to the category from transmissible subacute spongiform encephalopathies (ESST) also called “prion diseases”, the name of the protein in question. “Unlike other neurodegenerative diseases, Creutzfeldt-Jakob has the particularity of being able to affect both humans and animals“, specifies the neurologist and specialist in the disease Jean-Philippe Brandel. three forms of Creutzfeldt-Jakob disease (CJD):
- Sporadic CJD (85% of cases)
- Hereditary or genetic CJD (10% of cases)
- Acquired CJD (iatrogenic or variant CJD (mad cow disease) (5% of cases)
Creutzfeldt-Jakob disease in France
In France, Creutzfeldt-Jakob disease has mainly been publicized following health scandals. From 1992 to 2017, 3,073 deaths linked to certain or probable Creutzfeldt-Jakob disease have been recorded, according to Public Health France. Among these 3073 deaths:
- 2654 are linked to sporadic CJD
- 261 are linked to genetic CJD
- 131 are linked to iatrogenic CJD. (+4 cases linked to growth hormone in 1991)
- 27 deaths are related to variant CJD (v-CJD).
In all the countries of the world with a surveillance network for CJD, 1 to 2 cases per million inhabitants and per year are recorded.
mad cow crises
Two mad cow crises marked France in 1996 and 2000. In the 1980s, cases of bovine spongiform encephalopathy were discovered in cattle in the UK. These farm animals were contaminated after ingesting animal meal made from the remains of sick animals. In France, the first recognized case dates from the start 1991. Five years later, the transmissibility of this disease to humans through the consumption of beef is recognized. The human disease is called variant CJD (v-CJD). In addition to having had a profound effect on the general public, this food and health scandal led to the death ofa hundred people in the world and the slaughter of millions of cattle. “178 human cases have been recorded in Great Britain and 29 in France“, says Dr. Jean-Philippe Brandel.
The growth hormone scandal
In the early 1980s, more than a thousand children affected by stunted growth were administered growth hormones made from pituitary glands taken from cadavers, some of which were contaminated with the prion. Since 1991, about a hundred of them have declared iatrogenic Creutzfeldt-Jakob disease. A total of 123 people died as a result of this health scandal. Since this crisis, growth hormones have been produced synthetically.
The prion accumulates and leads to progressive destruction of the brain.
What are the causes ?
CJ disease is linked to accumulation in the brain of a prion protein (acronym for infectious protein particle) abnormal. The prion protein exists in healthy people in a normal form (PrPc). It is located on the surface of the cells of the nervous system and in particular of the neurons. In the case of a prion disease, it folds into an abnormal protein (PrPres). “It is what will cause the disease by depositing in aggregate form in the cells” explains Dr. Jean-Philippe Brandel. It will thus gradually destroy the brain. “The prion is the agent of transmission of CJD“, he adds. Each form of CJD has different causes.
► Sporadic CJD is the most common form of the disease (85% of cases prion diseases in humans). “In this case, we do not know why people declare the disease“, says Dr. Jean-Philippe Brandel. It affects people over 65 years old and can occur in isolation. Its evolution is very rapid.
► Genetic-hereditary CJD (10% of cases prion diseases) is the second most common form. The normal protein (PrPc) is encoded by a gene. But mutations of the gene carried by the chromosome 20 will give it an abnormal shape and thus cause CJD. The evolution is variable from 6 months to several years.
► Acquired CJD is the third form. In this case, the disease is transmitted following a treatment (iatrogenic form), such as growth hormones, or a graft of the dura mater or from contaminated bovine derivatives (v-CJD).
What are the symptoms ?
“The dementia is the first clinical sign of the CJD”, says Dr. Jean-Philippe Brandel. Intellectual, memory, language and gesture disorders come to reduce the autonomy of the patients quite quickly. muscle twitches called myoclonus also occur in the patient as well as a cerebellar syndrome. “Patients become ataxic and have walking disorders like drunk people“, adds the disease specialist. These motor signs gradually evolve towards an inability to walk. Patients may find themselves in a state of akinetic mutism unable to move or speak.
This disease which affects the central nervous system can be transmitted from derivatives of the central nervous system. The abnormal prion protein is the transmission agent. “It will contaminate normal proteins which will themselves become abnormal and contaminate other normal proteins. says Dr. Jean-Philippe Brandel. Hereditary formsfor their part, are transmitted by a mutated gene of the PrP protein. In humans, the gene is carried by the chromosome 20. “It is an autosomal dominant disease, that is to say that a single mutated allele is sufficient to declare the disease”, he adds. Acquired CJD is transmitted following a treatment (iatrogenic form), such as growth hormones, or a graft of the dura mater or from contaminated bovine derivatives (v-CJD or “mad cow”).
Is it hereditary?
In the genetic forms which represent 10% of prion diseases, ie approximately 15 patients per year, the disease is hereditary. First-degree relatives (brother, sister, father, mother) of a person with a genetic form have a 50% chance of carrying the mutated gene.
When the patient shows signs of dementia, three types of examinations are prescribed:
- brain MRI,
- an electroencephalogram,
- A lumbar puncture.
However, the certain diagnosis of CJD can only be made by studying the brain tissue rarely taken during the patient’s lifetime by biopsy but more often after autopsy.
Why use MRI?
“With MRI, one can observe an increase in the signal in the gray matter of the patient at the level of the cerebral cortex or the deep nuclei of the brain“, explains Dr. Jean-Philippe Brandel.
What treatments?
There are no curative or etiological treatments for CJD. That is to saywe can neither cure it nor stop its evolution. Only symptomatic treatments help calm patients’ muscle twitches, for example. “Neuroleptics or benzodiazepines in case of agitation may be administered to patients“, explains Dr. Jean-Philippe Brandel.
On average, life expectancy is estimated at 7 months.
What life expectancy?
The evolution of CJD is rapid. “Life expectancy is less than two years except in certain particular genetic forms“, indicates the neurologist. On average, it is estimated at 7 months.
Thanks to Dr Jean-Philippe Brandel, neurologist and specialist in Creutzfeldt-Jakob Disease