Progressive multifocal leukoencephalopathy—usually shortened to PML—is a rare, serious brain disease. It happens when a very common virus called the JC virus (JCV) wakes up in the body and attacks the brain’s white matter. White matter is the wiring that lets different parts of the brain talk to each other. When the virus harms this wiring, the myelin coating around nerve fibers gets destroyed. This damage is called demyelination.
The disease is called “progressive” because symptoms usually worsen over weeks to months, “multifocal” because many spots of damage appear in different brain areas, and “leukoencephalopathy” because it is a white-matter brain problem. PML almost always occurs in people whose immune system is weak, so the body cannot keep the JC virus under control.
Progressive multifocal leukoencephalopathy — usually shortened to PML — is a serious brain infection caused by the JC virus (JCV). Most adults quietly carry JCV without any problem. PML happens when the immune system becomes weak, the virus wakes up, and it damages the myelin (the insulation) around nerve fibers in the brain. That damage creates patchy white-matter lesions that can grow quickly and cause problems with movement, speech, vision, thinking, or balance. PML is rare but can be life-threatening if not handled fast. The single most important idea in treatment is rebuilding immune function (for example, with HIV treatment or by stopping certain immune-suppressing drugs) so the body can fight JCV again. NatureMedscape Reference
“Progressive” means symptoms often worsen over weeks to months. “Multifocal” means many separate spots in the brain can be involved at the same time. JCV infects oligodendrocytes (the cells that make myelin). When these cells die, electrical signals slow down or stop, and neurological symptoms appear. Diagnosis commonly relies on MRI patterns plus detecting JCV DNA in spinal fluid with sensitive PCR tests; modern “ultrasensitive” PCR can detect very low levels and is >95% sensitive when repeated if needed. Oxford AcademicPubMedPMCCleveland Clinic
Most adults have been exposed to JC virus at some point in life and carry it silently in the kidneys, bone marrow, or lymph nodes without any trouble. When the immune system is strong, the virus stays quiet. When the immune system becomes weak—from illnesses like advanced HIV infection, from blood cancers, from medications that suppress the immune system, or after organ or stem-cell transplant—the virus can reactivate. Once awake, it can travel to the brain, infect oligodendrocytes (the cells that make myelin), and cause patchy areas of demyelination. These patches interrupt normal brain signals and cause neurologic symptoms.
Who is most at risk
People are at highest risk if they have:
Very low immune defenses, especially low lymphocyte counts (the white blood cells that fight viruses).
Untreated or advanced HIV/AIDS, especially with low CD4 counts.
Blood cancers (like leukemia or lymphoma) or organ/stem-cell transplants where medicines reduce immunity.
Certain immune-modifying drugs used for multiple sclerosis (MS), autoimmune diseases, or cancers.
Long-term high-dose steroids or multiple different immune-suppressing drugs used together.
How PML differs from similar brain problems
Stroke is sudden and usually tied to blocked or bleeding blood vessels; PML is gradual and patchy.
Multiple sclerosis (MS) also damages myelin, but MS attacks come and go; PML usually worsens steadily without early fever or severe headache.
Brain tumors occupy space and often push on nearby tissue; PML lesions often have little mass effect and no strong swelling at first.
Brain abscesses are bacterial pockets and usually cause fever and more swelling; PML is viral and typically afebrile.
Types of PML
Classic PML in advanced HIV/AIDS
This was the most common form before modern HIV therapy. It occurs when CD4 counts drop very low. Lesions often involve both hemispheres and progress quickly without treatment of HIV.Hematologic malignancy–associated PML
People with leukemia, lymphoma, or myelodysplastic syndromes can develop PML because the disease and its treatments reduce immune surveillance.Transplant-related PML
After kidney, liver, heart, or stem-cell transplant, long-term immune-suppressing medicines can allow JC virus to reactivate.Drug-associated PML (immunotherapy- or biologic-related)
Some medications that alter lymphocyte trafficking or function raise PML risk. Notable examples include natalizumab (MS therapy) and certain B-cell–targeting monoclonal antibodies (e.g., rituximab, ocrelizumab), as well as some sphingosine-1-phosphate (S1P) modulators and other potent agents. Risk often rises with duration of therapy, prior immune suppression, and JC-virus antibody positivity.PML with immune reconstitution inflammatory syndrome (PML-IRIS)
When immunity improves rapidly—for example after starting effective HIV treatment or stopping an offending drug—the immune system can suddenly attack virus-infected brain areas, causing inflammation, new enhancement on MRI, and temporary clinical worsening, even as viral control improves.Cerebellar JC virus disease (JCV granule cell neuronopathy)
A JC-virus variant may primarily affect the cerebellum’s granule cells, leading to prominent balance and coordination problems, sometimes with fewer classic white-matter lesions.Asymptomatic or radiologically isolated PML
In patients under regular MRI monitoring (for example, some MS patients on high-risk drugs), early lesions may be found before obvious symptoms. Early detection can improve outcomes when the risky medication is stopped promptly.PML in people with minimal obvious immune suppression (very rare)
A few cases occur in people with subtle or unknown immune defects. Work-up often reveals unrecognized lymphopenia or a primary immune problem.
Causes of PML
PML is always tied to reactivation of JC virus in the setting of reduced immune control. Below are common “causes” or situations that allow the virus to cause disease.
Advanced HIV infection (AIDS)
Very low CD4 cells leave the brain unguarded, letting JC virus attack myelin-making cells.Untreated or late-treated HIV
If antiretroviral therapy is delayed or interrupted, the virus can reactivate and spread to the brain.Hematologic cancers (leukemia/lymphoma)
These diseases and their treatments lower lymphocyte counts and impair immune function.Solid-organ transplant
Long-term immune-suppressing drugs to prevent organ rejection reduce antiviral surveillance.Allogeneic stem-cell transplant
Intensive conditioning and graft-versus-host treatments deepen immune suppression.Multiple sclerosis therapy with natalizumab
This drug blocks immune cells from entering the brain, which can let JC virus reactivate there.B-cell–depleting therapies (e.g., rituximab, ocrelizumab, ofatumumab)
These medicines reduce antibody-producing cells, weakening control of latent viruses.S1P modulators (e.g., fingolimod, siponimod)
These trap lymphocytes in lymph nodes, leading to lower circulating lymphocyte numbers.Other potent immunotherapies or chemotherapy
Agents used for autoimmune disease or cancer can profoundly suppress immunity.Prolonged high-dose corticosteroids
Long courses dampen T-cell function, opening a window for JC virus.Combination immunosuppression
Using two or more immune-suppressing drugs raises cumulative risk.Primary (inborn) immune deficiency
Rare inherited problems with T-cell or B-cell function can allow PML.Severe lymphopenia from any cause
A very low absolute lymphocyte count reduces viral control in the brain.Older age with immunosenescence
The immune system naturally weakens with age, slightly increasing vulnerability.Chronic kidney disease or dialysis (indirect)
Uremia and frequent illness can blunt immunity, adding to risk in some patients.Malnutrition (indirect)
Poor protein and micronutrient status can weaken cell-mediated immunity.Sarcoidosis under immunosuppressive therapy
The disease plus its treatment can compound immune suppression.Autoimmune diseases needing strong immunosuppression
Conditions like lupus, vasculitis, or myositis may require medicines that lower viral control.Postpartum immune shifts (rare)
Rapid immune changes after pregnancy may unmask latent infections in rare cases.Unknown or mixed causes
Some patients have multiple overlapping factors or an unrecognized immune defect.
Common symptoms
Symptoms depend on where the brain is damaged. They usually build up over days to weeks and keep getting worse unless the underlying immune problem is fixed.
Weakness on one side of the body (hemiparesis)
Damage in motor pathways causes a heavy or clumsy arm/leg on one side.Poor coordination and balance (ataxia)
Cerebellar or white-matter injury causes staggering, wide-based gait, and frequent falls.Slurred or slow speech (dysarthria)
Trouble controlling tongue and facial muscles makes speech unclear.Trouble finding words or understanding speech (aphasia)
Left-hemisphere involvement affects language production or comprehension.Vision loss or blind spots (hemianopia or scotoma)
Occipital or optic pathway lesions cause part of the visual field to disappear.Numbness or tingling
Sensory pathway damage causes patchy numbness or pins-and-needles.Cognitive slowing and confusion
People feel slower, forgetful, or “foggy”, with trouble planning or focusing.Personality or behavior change
Frontal-lobe involvement leads to apathy, irritability, or poor judgment.Clumsiness of hands
Fine motor control worsens; buttons, keys, or writing become hard.Facial droop or asymmetry
Cortical or subcortical lesions can weaken facial muscles.Difficulty swallowing (dysphagia)
Brainstem or pathway damage causes coughing or choking with food.Vertigo or dizziness
Cerebellar involvement can cause a spinning sensation.Seizures (less common than in other diseases but possible)
Irritation of cortex by nearby lesions can trigger seizures.Headache (usually mild or absent early)
PML itself often causes little pain until inflammation or IRIS occurs.Rapid worsening after immune therapy change
If treatment is started or a drug is stopped and the immune system rebounds, IRIS can cause sudden swelling of lesions and symptom flare.
Diagnostic tests
Physical exam
Full neurologic mental-status exam
The clinician asks orientation, memory, attention, and language questions to spot cognitive slowing or aphasia. In PML, thinking may be slow, attention reduced, and language impaired if the left hemisphere is involved.Cranial nerve examination
Checks pupils, eye movements, facial strength, facial sensation, hearing, palate, and tongue. In PML, there may be visual-field cuts, partial eye-movement problems, facial weakness, or swallowing issues depending on lesion sites.Motor and reflex examination
Strength is graded in major muscle groups; tone and deep tendon reflexes are tested. PML often shows weakness, increased reflexes, or a Babinski sign on the affected side, signaling damage in the brain’s motor pathways.Gait and posture assessment
The clinician watches standing, walking, turning, and arm swing. In PML, gait may be unsteady, wide-based, or lopsided if one side is weak, and balance may worsen when multitasking.
Manual bedside tests
Finger-to-nose test
The patient touches their nose and the examiner’s finger back and forth. Past-pointing or shaky movement suggests cerebellar or connection problems seen in PML.Heel-to-shin test
Sliding the heel down the opposite shin checks leg coordination. Jerky or inaccurate movement points to cerebellar involvement.Rapid alternating movements (hands/feet)
The patient flips the hand palm-up/palm-down quickly or taps the foot rapidly. Slow, irregular rhythms reflect dysdiadochokinesia, common with white-matter or cerebellar lesions.Tandem gait and Romberg
Walking heel-to-toe challenges balance; standing with feet together and eyes closed tests proprioception and cerebellar control. PML often causes wobbling or stepping out.
Lab and pathological tests
Cerebrospinal fluid (CSF) JC-virus PCR
A lumbar puncture collects CSF. A polymerase chain reaction test looks for JC-virus DNA. A positive result strongly supports PML. If negative but suspicion is high, repeat testing may be needed.Quantitative JC-virus load in CSF
Measuring the amount of JC-virus DNA helps estimate disease activity and can help track response over time.CSF cell count, protein, and glucose
In PML, CSF is often normal or mildly abnormal (slight protein rise, few cells). Marked inflammation may suggest IRIS or an alternative diagnosis.Serum/CSF JC-virus antibody testing (index)
Detects prior exposure to JC virus. A positive antibody shows exposure, which is common in adults, and in some settings (e.g., MS therapy) a higher index helps risk-stratify, though it does not confirm PML by itself.HIV testing and CD4 count
If HIV status is unknown, testing is essential. A low CD4 count and high HIV viral load raise the chance of JC-virus reactivation and guide urgent HIV treatment.Absolute lymphocyte count and lymphocyte subsets
A low total lymphocyte count or reduced CD4/CD8/B-cell numbers point to immune suppression from disease or drugs, supporting the PML context.Rule-out CSF viral/bacterial PCR panel
Tests for HSV, VZV, CMV, toxoplasma, and others help exclude mimics of PML, since treatment differs.Brain biopsy with histology and JC-virus detection
Rarely needed when MRI and CSF PCR are clear. If diagnosis is uncertain, a small brain tissue sample can show typical demyelination, enlarged virus-infected oligodendrocyte nuclei, and JC-virus by immunohistochemistry or in-situ hybridization. This is the gold standard when noninvasive tests leave doubt.
Electrodiagnostic tests
Electroencephalogram (EEG)
Records brain electrical activity. In PML, EEG may show slow background rhythms in affected regions and can identify seizures if present.Visual evoked potentials (VEPs)
Measures the brain’s response to visual patterns. Delayed signals suggest optic pathway demyelination, which can accompany occipital or optic tract involvement.
Imaging tests
MRI brain with and without contrast (core test)
MRI is the most important imaging for PML. Typical findings are patchy, asymmetric white-matter lesions in the subcortical and periventricular regions, often hyperintense on T2/FLAIR, usually with little mass effect. Diffusion-weighted imaging (DWI) can show restricted diffusion at active lesion edges. Contrast enhancement is often absent early, but patchy or rim enhancement can appear, especially during PML-IRIS. The corpus callosum, parietal-occipital lobes, frontal lobes, and cerebellum may be involved. MR spectroscopy (part of MRI) may show low N-acetylaspartate (NAA) (neuron/axon loss), higher choline (membrane turnover), and sometimes lactate (metabolic stress).CT head (supportive, less sensitive)
CT may show low-density white-matter changes if lesions are large, but early disease is often missed. CT is useful if MRI is unavailable or contraindicated, or to exclude bleeding before lumbar puncture.
Non-pharmacological treatments (therapies & other supports)
These actions do not involve taking a specific drug to kill JCV. They aim to restore immunity, remove triggers, prevent complications, and rebuild function. Each item below includes what it is, why it’s used, and how it helps.
Immediate review of immune-suppressing medicines
What: Urgently assess monoclonal antibodies (e.g., natalizumab, rituximab), S1P modulators, chemotherapy, chronic steroids.
Why: Many PML cases happen during or after these drugs.
How: Stop the offending drug if PML is suspected/confirmed; this is usually the first step. NatureMDPIAmerican Academy of NeurologyPlasma exchange (PLEX) to remove certain antibodies
What: A blood-filtering procedure that pulls out drugs like natalizumab faster.
Why: Speeds drug clearance to allow immune cells back into the brain.
How: Several sessions over 1–2 weeks; note that evidence on benefit is mixed and IRIS risk can rise as immunity rebounds. PMCRapid initiation or optimization of HIV treatment (ART)
What: Start or intensify combination ART if the person has HIV.
Why: Immune reconstitution improves survival in HIV-related PML.
How: Begin guideline-based ART promptly; monitor for PML-IRIS. Medscape ReferencePMCIntensive neurological rehabilitation (PT/OT)
What: Physical and occupational therapy.
Why: PML often leaves weakness, spasticity, ataxia, and coordination problems.
How: Task-specific training to regain walking, transfers, self-care; splints and mobility aids reduce falls.Speech and swallow therapy
What: Speech-language pathology support.
Why: Brain lesions can affect speech and swallowing, raising aspiration risk.
How: Swallow exercises, diet texture modification, and communication strategies.Cognitive rehabilitation
What: Structured programs for attention, memory, and executive function.
Why: White-matter injury can impair thinking and multitasking.
How: Compensatory tools (planners, phone reminders) and repetitive cognitive drills.Vision and neuro-optometry care
What: Prism lenses, visual scanning training.
Why: PML may cause visual field cuts or tracking issues.
How: Tailored visual rehab to reduce reading, driving, and mobility problems.Seizure safety plan and trigger control
What: Education and home safety steps for anyone with seizures or high risk.
Why: Brain lesions increase seizure risk.
How: Supervised bathing, avoid heights, sleep hygiene, driving restrictions per local rules.Nutritional support
What: Dietitian-guided energy and protein plans; texture changes if dysphagia.
Why: Malnutrition worsens recovery; dysphagia raises pneumonia risk.
How: Calorie/protein targets; consider temporary feeding tube if unsafe swallow.Pressure-injury and DVT prevention
What: Repositioning schedules, cushions, and mobility plans.
Why: Weakness and immobility increase skin and clot risks.
How: Early mobilization, compression, and skin checks.Mental health counseling
What: Psychotherapy and support groups for patient and caregivers.
Why: Anxiety/depression are common after sudden neurological disability.
How: CBT, coping skills, caregiver respite.Caregiver training and respite planning
What: Teach safe transfers, feeding, medication organization.
Why: Reduces falls, aspiration, burnout.
How: In-home training plus periodic respite services.Home safety modifications
What: Rails, ramps, non-slip flooring, bathroom aids.
Why: Prevents falls and injuries.
How: Occupational therapy home visit to tailor changes.Vaccination review (non-live vaccines)
What: Stay current on inactivated vaccines (e.g., influenza, pneumococcal).
Why: Preventing other infections helps protect fragile recovery.
How: Coordinate with the treating team; avoid live vaccines if immunocompromised.Sleep optimization
What: Treat sleep apnea/insomnia.
Why: Sleep affects cognition, mood, and seizure threshold.
How: Sleep study if indicated; structured sleep routines.Fatigue management & energy conservation
What: Pacing, scheduled rests, and prioritizing tasks.
Why: Neurological fatigue is common and disabling.
How: OT-guided daily plans.Regular MRI and clinical monitoring in high-risk patients
What: Ongoing imaging and neuro exams during and after high-risk drugs.
Why: Early detection improves outcomes; CSF JCV testing is repeated if initial is negative but suspicion stays high.
How: Programmed MRI and ultrasensitive CSF PCR when needed. Cleveland ClinicTelemedicine and rapid-access review
What: Quick check-ins to catch early changes.
Why: Small neurological shifts can signal new lesions or IRIS.
How: Standardized symptom checklists and video exams.Advance-care planning and palliative care when appropriate
What: Discuss goals, preferences, and symptom relief options.
Why: PML can be severe; patient values should guide choices.
How: Early palliative consults—in addition to active treatment.Multidisciplinary case conferences
What: Neurology, infectious disease, immunology, rehab, nursing, social work.
Why: Decisions (e.g., stopping an MS biologic, starting immune therapies) have trade-offs.
How: Team meetings to align on risks, benefits, and sequencing.
Drug treatments
Important: doses below are typical adult examples, not personal medical advice. PML care is complex—always individualized by your specialist team.
Combination antiretroviral therapy (ART) for HIV-related PML
Class: Integrase-based combination (example: dolutegravir + tenofovir + emtricitabine).
Typical dose/time: e.g., dolutegravir 50 mg once daily + tenofovir disoproxil 300 mg once daily + emtricitabine 200 mg once daily (many other guideline-approved options).
Purpose/mechanism: Restores immune function so the body controls JCV.
Side effects: Variable (nausea, insomnia, kidney/bone issues with specific drugs).
Evidence note: Core of PML therapy in HIV; improves outcomes; monitor for IRIS after starting. Medscape ReferencePMCCorticosteroids for PML-IRIS (not for routine PML)
Class: Anti-inflammatory (e.g., methylprednisolone/prednisone).
Typical dose/time: Common practices include methylprednisolone 500–1,000 mg IV daily for 3–5 days, then taper with oral prednisone (actual plan individualized).
Purpose/mechanism: Temporarily dampens damaging inflammation when immune function rebounds.
Side effects: High blood sugar, infection risk, mood changes.
Evidence note: Guidelines: use steroids when IRIS threatens function or life. ClinicalInfoPembrolizumab (off-label)
Class: PD-1 checkpoint inhibitor (immunotherapy).
Typical dose/time: Case series used 2 mg/kg IV every 4–6 weeks for several cycles.
Purpose/mechanism: Lifts immune “brakes,” potentially boosting anti-JCV T-cell activity.
Side effects: Immune-related inflammation (thyroid, liver, lungs, skin).
Evidence note: Mixed results in small studies/case series; used selectively at expert centers. New England Journal of MedicineAmerican Academy of NeurologyPMCNivolumab (off-label)
Class: PD-1 checkpoint inhibitor.
Typical dose/time: 3 mg/kg IV every 2 weeks has been reported in case reports.
Purpose/mechanism: Same concept as pembrolizumab.
Side effects: Immune-related adverse events (colitis, hepatitis, pneumonitis, endocrinopathies).
Evidence note: Individual successes reported; still experimental. PMCCDC StacksMirtazapine (off-label)
Class: Antidepressant; 5-HT2A receptor antagonist.
Typical dose/time: 15–45 mg by mouth at night.
Purpose/mechanism: JCV uses 5-HT2A receptors to enter glial cells; blocking them may reduce viral entry.
Side effects: Sedation, weight gain, dry mouth.
Evidence note: Mechanistic support and case reports; not a proven cure. PMCOxford AcademicMefloquine (off-label, controversial)
Class: Antimalarial.
Typical dose/time: Various regimens in reports; no clear standard, and a clinical study did not show benefit.
Purpose/mechanism: In-vitro activity against JCV replication.
Side effects: Neuropsychiatric effects, dizziness, GI upset.
Evidence note: Randomized/controlled data have not confirmed efficacy; use is uncommon. PMCIntravenous immunoglobulin (IVIG) (select cases)
Class: Immune-modulating pooled antibodies.
Typical dose/time: Highly variable; case reports used low-dose, long-term schedules.
Purpose/mechanism: May support humoral immunity and modulate inflammation.
Side effects: Headache, thrombosis risk, aseptic meningitis (rare).
Evidence note: Case-level evidence only. BioMed CentralMaraviroc (adjunct for IRIS in select cases; off-label)
Class: CCR5 antagonist (HIV entry inhibitor).
Typical dose/time: Case use around 600 mg/day; regimens vary.
Purpose/mechanism: May reduce IRIS-related inflammation by blocking CCR5-mediated immune cell trafficking.
Side effects: Liver enzyme changes, cough, hypotension.
Evidence note: Anecdotal/observational; specialist use only. SpringerLinkAntiseizure medicines (symptom control)
Class: e.g., levetiracetam.
Typical dose/time: Often started at 500 mg twice daily, titrated as needed.
Purpose/mechanism: Controls seizures caused by cortical involvement.
Side effects: Somnolence, mood changes (varies by drug).
Evidence note: Symptomatic, not antiviral; commonly needed in PML care.Spasticity and mood medications (symptom control)
Class: Baclofen/tizanidine for spasticity; SSRIs for depression/anxiety when mirtazapine isn’t chosen.
Typical dose/time: Baclofen often 5 mg three times daily, titrated; SSRI doses vary (e.g., sertraline 50 mg daily).
Purpose/mechanism: Improve comfort and function, enabling rehab.
Side effects: Muscle weakness (baclofen), GI/sexual effects (SSRIs).
Evidence note: Supportive care improves quality of life and rehab participation.
Dietary molecular supplements
There is no supplement that treats or cures PML. These are general immune-health supports your clinician may consider if safe for you. Always check for drug interactions.
Vitamin D3 (cholecalciferol) — 1,000–4,000 IU/day. Supports T-cell function; correct deficiency.
Vitamin B12 (methylcobalamin) — 1,000 mcg/day if low. Supports myelin and nerve health.
Omega-3 (EPA+DHA) — 1–2 g/day. Anti-inflammatory; may aid neuronal membranes.
Vitamin C — 250–1,000 mg/day. General antioxidant support.
Zinc — 15–30 mg/day (short courses). Needed for lymphocyte function; avoid long-term excess.
Selenium — 100–200 mcg/day. Antioxidant cofactor supporting immunity.
Magnesium — 200–400 mg/day. Helps muscle tone and sleep; watch for diarrhea.
Folate (or L-methylfolate) — 400–800 mcg/day. Supports myelin and hematologic health.
Probiotics — ≥10⁹ CFU/day. Gut-immune axis support; choose reputable brands.
Curcumin (with piperine) — 500–1,000 mg/day. Anti-inflammatory adjunct; monitor for GI upset.
Regenerative & cellular options
Recombinant human interleukin-7 (rhIL-7; CYT107)
Function: Expands and energizes T cells that fight JCV.
Mechanism: Cytokine that promotes T-cell survival and proliferation.
Dose used in reports: 10 µg/kg IM weekly × 3 (examples).
Evidence: Case reports and small series show lymphocyte rises and clinical/MRI stabilization in some patients. PMCJAMA NetworkOxford AcademicPembrolizumab (PD-1 inhibitor)
Function: Releases immune “brakes” on exhausted T cells.
Mechanism: Blocks PD-1 to enhance antiviral T-cell responses.
Dosing used in PML reports: 2 mg/kg IV every 4–6 weeks for several cycles.
Evidence: Case series with mixed outcomes; used in expert centers with careful monitoring. New England Journal of MedicineNivolumab (PD-1 inhibitor)
Function/mechanism: Same pathway as pembrolizumab.
Dosing in reports: 3 mg/kg IV every 2 weeks for a limited number of doses.
Evidence: Case reports of benefit; still investigational for PML. PMCAdoptive JCV-specific T-cell therapy (personalized or third-party)
Function: Infuse lab-prepared T cells that recognize and attack JCV.
Mechanism: Cellular immunotherapy targeting viral antigens.
Dosing: Given in infusion cycles (protocols vary).
Evidence: Increasing real-world/series reports showing clinical and MRI improvements in select patients. Availability is limited to specialized programs/trials. American Academy of NeurologyPubMedJAMA NetworkBK virus-specific T cells (cross-reactive to JCV)
Function: Off-the-shelf virus-specific T cells sometimes used when JCV-specific cells are not available.
Mechanism: T-cell cross-reactivity within polyomaviruses.
Evidence: Case series suggest possible benefit; still investigational. ASTCT JournalCombination immunotherapy approaches
Function: Carefully sequenced PD-1 blockade + virus-specific T cells or IVIG + mirtazapine, tailored to the patient.
Mechanism: Synergistic immune re-activation with antiviral entry blockade or humoral support.
Evidence: Early reports and small series only; decisions are individualized in expert centers. American Academy of NeurologyBioMed Central
Procedures/surgeries
Stereotactic brain biopsy
Why: When MRI + CSF testing is inconclusive, biopsy can confirm PML by showing JCV-infected cells and demyelination.
How: Needle biopsy using imaging guidance; used only when necessary. PubMedCentral venous catheter placement for PLEX
Why: Needed to safely perform plasma exchange for drug removal (e.g., natalizumab).
How: Short procedure to place a large-bore catheter.Percutaneous endoscopic gastrostomy (PEG) tube
Why: Severe swallowing problems and weight loss.
How: Feeding tube through the abdomen to maintain nutrition safely.Tracheostomy
Why: Rarely, when airway protection and long-term ventilation are needed due to severe neurologic impairment.
How: Surgical airway to improve breathing comfort and safety.Intrathecal access (e.g., Ommaya reservoir) — uncommon
Why: Occasionally used in research settings to deliver investigational agents directly into CSF.
How: Small surgical reservoir placed under the scalp; not standard care.
Prevention strategies
If you have HIV, start and stick with ART. Keeping CD4 counts healthy is the best defense against PML. Medscape Reference
Before starting natalizumab for MS, check JCV antibody status and risk. Discuss duration limits and risk calculators with your neurologist. MSARD Journal
Consider extended-interval dosing of natalizumab (e.g., every 6 weeks) if appropriate. Large real-world data suggest similar MS control with lower PML risk. ScienceDirect
Avoid stacking immunosuppressants (e.g., combining biologics with high-dose steroids) unless essential and carefully supervised. Nature
For S1P modulators and other MS drugs, follow strict monitoring plans. Some agents carry PML risk; MRI and clinical surveillance catch early signs. American Academy of Neurology
Report new neurological symptoms immediately (language changes, visual loss, clumsiness, new weakness). Early action matters.
Keep vaccinations up to date (inactivated vaccines). Preventing other infections helps preserve immune reserves during recovery.
Manage other health problems (diabetes, kidney disease, malnutrition) that blunt immune responses.
Use the lowest effective steroid dose for the shortest time if you need steroids for other conditions.
Schedule regular follow-up with neurology and infectious-disease specialists if you are on or coming off high-risk medicines.
When to see a doctor urgently
New or worsening neurological symptoms (speech issues, weakness, clumsiness, tremor, vision changes, personality change).
Any new neuro symptom while on natalizumab, rituximab/ocrelizumab, S1P modulators, or after chemotherapy.
After starting HIV treatment if you feel rapidly worse neurologically (possible IRIS). PMC
Seizures, severe headaches, or repeated falls.
Trouble swallowing (choking, weight loss) or breathing.
What to eat — and what to avoid
Eat: protein-rich meals (eggs, fish, lean meats, tofu, dairy/legumes) to support muscle maintenance during rehab.
Eat: colorful fruits/vegetables daily for antioxidants and fiber.
Eat: omega-3 sources (fatty fish, flax, walnuts) for general anti-inflammatory support.
Eat: whole grains and adequate fluids to help bowel regularity if mobility is limited.
Eat: yogurt/fermented foods (if tolerated) to support gut health.
Avoid: heavy alcohol (worsens balance, sleep, and immunity).
Avoid: ultra-processed foods high in sugar/salt that worsen fatigue and blood pressure.
Avoid: grapefruit/Seville orange if you’re on drugs with known interactions (ask your pharmacist).
Avoid: unpasteurized foods if you are immunocompromised.
Avoid: unnecessary supplements or herbals without checking for drug interactions.
FAQs
1) Is PML contagious?
No. You can’t “catch” PML from someone. JCV is common, but PML happens when your own virus reactivates during immune weakness. Nature
2) What usually triggers PML?
Severe immune suppression—untreated HIV, cancer therapies, or certain MS/autoimmune biologics (e.g., natalizumab, anti-CD20 antibodies, some S1P modulators). NatureMDPIAmerican Academy of Neurology
3) How is PML diagnosed?
Typical brain MRI patterns plus JCV DNA in spinal fluid by PCR. If the first test is negative but suspicion is high, doctors may repeat an ultrasensitive PCR or, rarely, perform a brain biopsy. Cleveland ClinicPMCPubMed
4) Is there a cure?
There’s no specific antiviral cure. Rebuilding immunity is the cornerstone and can lead to stabilization or improvement in some people. Medscape Reference
5) What is PML-IRIS?
As the immune system recovers, it may overreact against JCV-infected tissues, temporarily making symptoms worse. Doctors sometimes use steroids to control dangerous inflammation. ClinicalInfo
6) Do drugs like mirtazapine or mefloquine work?
Mirtazapine blocks a receptor JCV uses to enter cells and has case-level support; mefloquine looked promising in the lab but did not help in a clinical study. Neither is a proven cure. PMC+1
7) What about immunotherapy (pembrolizumab/nivolumab)?
These PD-1 inhibitors can sometimes help by reviving antiviral T cells, but results vary and side effects are real. They’re off-label and reserved for specialist centers. New England Journal of MedicinePMC
8) Are there promising cellular therapies?
Yes—JCV-specific or BK-virus–specific T-cell infusions are being used at some centers with encouraging reports, though access is limited. American Academy of NeurologyASTCT Journal
9) If PML occurred on natalizumab, should the drug be removed quickly?
Stopping the medicine is standard; plasma exchange is often used to clear it faster, but its benefit is uncertain and must be weighed against IRIS risk. PMC
10) How fast can PML progress?
Symptoms usually worsen over weeks to months, which is why early recognition and action are critical. Nature
11) What is my long-term outlook?
Outcomes vary widely and depend on how quickly immune function is restored, how extensive the brain lesions are, and whether complications like IRIS occur. ART has improved survival in HIV-related PML. Medscape Reference
12) Can PML recur?
If immunity drops again (for example, stopping ART or restarting high-risk immunosuppression), reactivation is possible; careful follow-up is key.
13) Are there vaccines to prevent JCV or PML?
No JCV vaccine exists at this time.
14) What should families watch for at home?
Any sudden change in speech, vision, balance, personality, swallowing, or new seizures—contact your team right away.
15) Should everyone on natalizumab switch drugs to avoid PML?
Not necessarily. Risk depends on JCV antibody status, treatment duration, prior immunosuppressants, and dosing schedule; some people use extended-interval dosing to lower risk while maintaining control of MS. Decide with your neurologist. MSARD JournalScienceDirect
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The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: August 15, 2025.
