Progressive Multifocal Leukoencephalopathy (PML)

Page Contents

1 WHAT IS IT?
2 WHAT CAUSES IT?
3 WHY IS IT A PROBLEM?
4 WHAT MAKES US SUSPECT IT?
5 CLINICAL WORKUP
6 AT WHAT POINT DO WE CONFIDENT IN MAKING THE DIAGNOSIS?
7 HOW DO WE TREAT IT?
8 HOW WELL DO THE PATIENTS DO?
9 WAS THERE A WAY TO PREVENT IT?
10 OTHER FACTS?
11 FURTHER READING

WHAT IS IT?

Progressive multifocal leukoencephalopathy (PML) is a viral disease that is characterized by inflammation and progressive damage of the white matter of the brain.

WHAT CAUSES IT?

This condition is caused by the John Cunningham (JC) virus. This virus is normally present and suppressed by the immune system, however in situation of chronic immunosuppression it can be allowed to re-activate. Specific causes of immunosuppression can include:

AIDS/HIV
Hodgkin disease
Other lymphomas/leukemias
Immunosuppressant medications: Rituximab, N atalizumab

WHY IS IT A PROBLEM?

The re-activatoin of the JC virus results in the injury of oligodendrocytes and demyelination of nerve axons. Given the important role of myelin in nerve conduction this is very problematic condition.

The loss of the myelin sheath around nerve axons will decrease the speed at which signals travel along the axon (source)

WHAT MAKES US SUSPECT IT?

Risk factors

CD4 counts <200/mm³, Rituximab/Natalizumab

Initial Presentation

Visual loss
Weakness
Dementia/impaired cognition

History Of Present Illness

Rapid progression: this condition will worsen quickly

Impaired cognition can include memory issues.

Physical Exam Findings

The physical exam can be quite variable (presentation will depend on the exact patter of demyelination). However some more common findings can be:

Visual field abnormalities
Hemiplegia

CLINICAL WORKUP

Lumbar puncture is often unremarkable (no gross changes to general CSF values).

CSF PCR can detect the JC virus.

Head MRI can show non enhancing areas of demyelination.

T2 MRI images showing demyelination caused by PML (source)

Brain biopsy can be used to diagnose this condition if the MRI and CSF PCR are not definitive.

AT WHAT POINT DO WE CONFIDENT IN MAKING THE DIAGNOSIS?

Our threshold for making the diagnosis can vary, however generally speaking it is the CSF PCR or brain biopsy that can be used to more definitively state that the JC virus is responsible for the patient’s condition (PCR is generally the testing modality of choice).

With that in mind, in a certain clinical setting, characteristic findings on the MRI may be enough to make the diagnosis (especially in a patient with a low CD4 count).

HOW DO WE TREAT IT?

There are no targeted therapies for PML however the goal of therapy is to restore the immune status of the host.

HOW WELL DO THE PATIENTS DO?

This is a serious condition with a high mortality rate

WAS THERE A WAY TO PREVENT IT?

Maintaining CD4 counts in AIDS by adhering to treatments can prevent this condition from occurring.

OTHER FACTS?

Any region of the CNS may be involved, but optic nerve or spinal cord involvement are rare.