Evidence of an alteration in the white matter that surrounds neurons, progressive multifocal leukoencephalopathy is a neurological disease that simultaneously affects several regions of the brain and progresses gradually. Its causes are multiple. 

Neurons (nerve cells in the brain) are extended by nerve fibers, called axons, which will connect with others in the brain through synapses (ends of the axon). These nerve fibers are surrounded by a sheath (myelin) which isolates them from each other and is part of the white matter of the brain.

Progressive multifocal leukoencephalopathy (PML) testifies to an alteration in several places of the brain of this sheath which surrounds the axons, causing short circuits between them. These short circuits are at the origin of the dysfunctions of the brain in relation to the mobilization of the muscles, of the cerebral activity (thought or cognitions) and of the nerve fibers of the sensitivity. Hence the occurrence of paralysis, disturbances of thought and sensitivity.

This degenerative neurological disease is most often progressive, evolving in spurts or very slowly and simultaneously affecting several sites of the brain (multifocal). Its causes are multiple and its symptoms depend on the sites affected.

The causes of progressive multifocal leukoencephalopathy (PML) are many and varied in nature:

Hereditary or genetic

Sometimes starting quite early as in certain syndromes or diseases such as Cadasil’s disease linked to a genetic mutation, Childhood Ataxia syndrome at the origin of cavities in the white matter of the brain by the destruction of myelin, multiple sclerosis (MS) which is occurs on a hereditary basis and also sometimes causes cavities (cavitary form of MS), or degenerative diseases of the brain such as fragile X syndrome or mitochondrial disease.

Vascular origin

It is a vascular dementia caused by damage to the small vessels of the brain (microangiopathy), related to age, old and unbalanced high blood pressure or diabetes.

Of toxic origin 

By taking certain drugs such as methotrexate used in the treatment of certain cancers or autoimmune diseases (rheumatoid arthritis or RA, etc.), nitric oxide poisoning (heating with defective gas) or inhaling heroin vapors (addictive use). Radiation therapy can also alter the white matter in the brain.

Of degenerative origin

It is linked to inflammatory processes affecting the nervous system such as MS, leucoaraiosis, or Alzheimer’s disease, sometimes of hereditary origin but not always, with the latter disease of accumulation of deposits that will disrupt neuronal transmission ( amyloid deposits and neurofibrillary degeneration associated with the presence of proteins in the brain, beta-amyloid peptide and tau protein).

Infectious origin

Rarely in viral infections such as papillomavirus (JC virus) or AIDS (2 to 4% of HIV + people).

Symptoms of progressive multifocal leukoencephalopathy (PML) vary depending on the areas affected and the cause of this degenerative process in the brain:

• feeling weak, difficulty speaking or thinking at the onset of the disease;
• intentional tremor (cerebellar syndrome) and gait disturbances in fragile X syndrome or mitochondrial disease, disorders of voluntary coordination, symptoms expressing early in these hereditary or genetic pathologies and progressing gradually and inevitably …;
• psychiatric disorders during degeneration of vascular origin, often occurring later in the elderly with mood disorders, cognitive disorders (temporo-spatial disorientation, memory disorders), sometimes delusions and confusion;
• impaired sensitivity and motor skills in degenerations of toxic origin;
• cognitive decline in brain degeneration such as Alzheimer’s disease with impaired memory, orientation, attention, problem solving, planning and organization, thinking;
• the risk of cerebrovascular accident (stroke) is increased in progressive multifocal leukoencephalopathy;
• migraines and epileptic seizures.

The clinical signs are already suggestive of this pathology, but it will be brain imaging such as Magnetic Resonance Imaging (MRI) that will make it possible to find lesions suggestive of the white matter of the brain.

The detection of the JC virus by lumbar puncture is sometimes indicated in the event of suspicion of progressive multifocal leukoencephalopathy of viral origin.

The diagnosis of AIDS is usually already made and if not, it should be researched.

Treatment of progressive multifocal leukoencephalopathy is that of the cause:

• search for toxic causes (drugs, heroin, etc.) and eradicate them; 
• confirmation of the diagnosis of cerebral degeneration for Alzheimer’s disease, MS, leukoaraiosis, dementia of vascular origin.

The lesions of the white matter will remain irreversible and psychosocial support and cognitive stimulation will slow the progression of this disease which sometimes evolves over several years.