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PLEX: Plasma Exchange for MS (Multiple Sclerosis)

Plasma Exchange for MS

Plasma Exchange for MS

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system. It damages the myelin sheath that surrounds and protects nerve fibers.

During an acute exacerbation of MS, patients may experience a sudden onset of symptoms, including loss of vision, weakness of one or more parts of the body such as the hands, legs, arms, etc, and difficulty in moving normally as a result of loss of coordination and balance.

Plasma exchange is one of the three modalities used to treat severe flares of MS, along with high-dose pulse methylprednisolone therapy and IVIG therapy for five days.

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What is Plasmapheresis?

Plasmapheresis is a procedure by which the plasma is cleared of important cells and factors such as immunoglobulins that are present in abundance in patients with MS.

The albumin and plasma without immunoglobulins and antibodies are then returned back and reinfused to the patient.

Thus, while corticosteroids and other immunomodulatory drugs act very slowly by inhibiting the formation of antibodies, plasmapheresis rapidly acts by removing all the antibodies responsible for damaging the nerves.

The use of plasma exchange for the treatment of MS is based on the hypothesis that removing antibodies and other inflammatory factors from the plasma may help reduce inflammation and damage to the myelin sheath.

Plasma exchange has been used in the treatment of several other autoimmune disorders, including Guillain-Barre syndrome, autoimmune encephalitis, lupus nephritis, immune thrombocytopenic purpura, thrombotic thrombocytopenic purpura, neuromyelitis optica, and severe falciparum malaria.

Use of plasma exchange in several conditions:

Autoimmune Disorder

Indication for Plasma Exchange

Guillain-Barre Syndrome A severe or rapidly progressive disease, ineffective response to IVIG
Autoimmune Encephalitis A severe or rapidly progressive disease, ineffective response to immunotherapy
Lupus Nephritis Severe or refractory nephritis, thrombotic microangiopathy
Immune Thrombocytopenic Purpura Severe bleeding or platelet counts <20,000/mm3
Thrombotic Thrombocytopenic Purpura Severe or refractory disease, neurological involvement
Neuromyelitis Optica Severe or relapsing disease, ineffective response to immunotherapy
Severe Falciparum Malaria Severe or complicated disease, ineffective response to antimalarial drugs
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Indications of Plasma exchange for MS (Multiple sclerosis):

Plasma exchange is helpful in managing:

  • Acute flares of MS when high-dose methylprednisolone therapy fails to produce the desired response.
  • Patients with relapsing multiple sclerosis and CNS demyelinating diseases
  • In some cases, patients may be intolerant to high-dose steroids or have contraindications to their use.

Indications for plasma exchange in MS and related conditions

Condition

Indications for Plasma Exchange

MS Acute Flares Inadequate response to high-dose methylprednisolone therapy
Relapsing MS N/A
CNS Demyelinating Diseases Acute disseminated encephalomyelitis (ADEM), Transverse myelitis, Optic neuritis, and Neuromyelitis Optica
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Efficacy of PLEX (Plasma exchange) for MS:

Clinical trials have shown that plasma exchange (PLEX) can be effective in the treatment of multiple sclerosis (MS), particularly in cases where high-dose corticosteroid therapy has failed. The following studies provide evidence for the efficacy of PLEX in managing MS.

Study 1: Randomized trial comparing PLEX with sham treatment [Ref]

This study involved 116 MS patients experiencing acute exacerbations, who were randomized to receive either 11 courses of PLEX or placebo treatment over eight weeks.

All patients were also treated with oral cyclophosphamide and adrenocorticotrophic hormone (ACTH).

Although, there were no clinically significant differences between the two modalities of treatment, patients in the PLEX therapy did well overall.

Study 2: Randomized trial of PLEX for MS after methylprednisolone failure [Ref]

In this trial, 22 patients with severe neurological deficits from various CNS inflammatory disorders, including MS, who were refractory to high-dose corticosteroids were enrolled.

These patients were randomized to receive either PLEX or placebo treatment. The results showed that patients who received PLEX were more likely to have a sustained clinical response.

Study

Participants

Treatment

Results

1 116 MS patients PLEX vs. sham treatment No overall difference, but the trend in favor of PLEX at one month
2 22 patients with severe neurological deficits PLEX vs. sham treatment PLEX group is more likely to improve, sustained improvement even after treatments stopped

These clinical trials provide evidence for the effectiveness of PLEX in the management of MS, particularly in cases where high-dose corticosteroids have failed.

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Frequency to perform PLEX:

Frequency of PLEX

There are no established guidelines for the frequency of PLEX, and it mainly depends on clinical judgment. Patients typically receive three to seven sessions based on clinical requirements and response, with each session taking 2-4 hours. PLEX can also be used in MS patients who develop complications like progressive multifocal leukoencephalopathy secondary to the use of Natalizumab. In this case, five sessions are necessary as per one guideline.

Preparation of the Patient for PLEX

A central line is placed by injecting a local anesthetic. The patient is asked to lie down with the head elevated or flat as the patient feels comfortable.

Pulse and blood pressure are monitored frequently (every 15 minutes or so) during the procedure, especially during the first hour of the infusion.

Patients are monitored for clinical features of hypocalcemia such as tetanic spasms and for signs of dehydration manifesting as hypotension.

Technique

The following steps are involved in performing therapeutic PLEX using centrifugation-based equipment like the Spectra Auto PBSC:

First, we need to take out any heparin from two tubes. We will then take a sample of the patient’s blood to check it. We will also clean the tubes with some normal saline by flushing them.

We will then measure the patient’s height and weight, and use that to figure out how much plasma we need to replace. We will choose a product to use and figure out how fast to spin it in a machine.

We will put the patient’s blood into the machine, which will spin it around to separate the different parts. We will throw away one part of the blood and keep another part, which we will give back to the patient along with a different liquid called albumin or fresh frozen plasma.

After we take out the right amount of plasma, we will put heparin back into the tubes to stop them from getting blocked until we need to use them again. Finally, we will check the patient’s fibrinogen levels to make sure everything is okay.

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Type of Patients Who Will Have the Most Benefit:

Almost half of the patients experience moderate to marked recovery through the use of PLEX. Marked improvement can be seen in patients who have NMO (Neuromyelitis Optica), a variant of MS, and the Marburg variant.

Plasmapheresis in Guillain-Barré Syndrome

Guillain-Barré syndrome (GBS) is not an uncommon disorder. However, unlike MS, in which the immune system attacks the person’s neurons of the brain and spinal cord, in GBS, the neurons of the peripheral nervous system are affected.

The peripheral nervous system includes all the nerves that come out of the brain and spinal cord and supply the muscles, skin, and tissues.

High-dose intravenous immunoglobulin (IVIG) and plasmapheresis are both effective treatments for GBS.

Plasmapheresis may be more effective in patients with severe GBS, those who cannot tolerate IVIG or those who do not respond to IVIG. The American Academy of Neurology recommends plasmapheresis as a first-line treatment for GBS.

Plasmapheresis in Myasthenia Gravis

Myasthenia gravis (MG) is another immune-mediated inflammatory disease. Unlike MS and GBS in which the neurons of the brain and the peripheral nervous system are affected, in Myasthenia Gravis, the neuromuscular junction is affected.

It is characterized by weakness, fatigue, and inability to look up as the day passes. Patients feel normal in the morning and as the day passes, the weakness worsens.

Plasmapheresis can be an effective treatment for MG, particularly in patients who have a sudden worsening of symptoms or who do not respond to other treatments.

In a randomized controlled trial, plasmapheresis was found to be more effective than IVIG in patients with severe MG exacerbations. Plasmapheresis is also useful as a preoperative treatment for MG patients who require surgery.

Plasmapheresis in Neuromyelitis Optica

For patients with NMO, plasmapheresis has been found to be effective in improving symptoms, especially when high-dose corticosteroids are not sufficiently effective.

Plasmapheresis has also been found to be effective in patients with ADEM.

Other conditions where Plasmapheresis may be effective are catastrophic antiphospholipid syndrome, rapidly progressive crescentic glomerulonephritis, HUS (hemolytic uremic syndrome), and TTP (thrombotic thrombocytopenic purpura and PML (progressive multifocal leukoencephalopathy).

Indications for plasmapheresis in various neurological conditions

Neurological Condition

Indication for Plasmapheresis

Guillain-Barré syndrome First-line treatment; may be more effective in severe cases or in patients who cannot tolerate IVIG
Myasthenia gravis Treatment for a sudden worsening of symptoms or lack of response to other treatments; preoperative treatment for patients requiring surgery
Neuromyelitis Optica Effective if the acute attacks do not respond to oral immunosuppressive drugs alone.
Acute disseminated encephalomyelitis Plasmapheresis has been shown to be effective in case reports.
PML (Progressive multifocal leukoencephalopathy) Five sessions are necessary as per one guideline
Natalizumab-associated PML Can be used in patients who develop complications like progressive multifocal leukoencephalopathy secondary to the use of Natalizumab in MS

Neuroinflammatory Conditions for Which Plasmapheresis is Effective

Condition

Effectiveness of PLEX

Neuromyelitis Optica (NMO) Effective
Acute disseminated encephalomyelitis Effective
Progressive multifocal leukoencephalopathy (PML) associated with treatment with a monoclonal antibody Effective
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Requirements for Plasmapheresis in MS:

As mentioned earlier, plasmapheresis is a specialized medical procedure that requires specific equipment and trained personnel. The following table summarizes the requirements for plasmapheresis in MS:

Requirement

Description

Setting Plasmapheresis is typically performed in a plasmapheresis unit, either as an outpatient or inpatient procedure
Intravenous Catheter Large-bore catheters are needed to provide a free flow of blood flow through the machine.
Hospitalization Hospitalized is usually required because of associated complications
Insurance Coverage Insurance coverage may vary depending on the patient’s plan and the indication for plasmapheresis

Requirements for Plasmapheresis Treatment in Patients with CNS Demyelination

Requirement

Description

Procedure location Plasmapheresis unit
Intravenous catheters Large-bore
Catheter placement Typically placed by Interventional Radiology
Hospitalization Hospitalized is required because of the associated complications
Insurance coverage May be an issue
Pre-treatment hydration Patients are asked to drink plenty of water (6-8 glasses of clear fluids daily for three days before the procedure and during the treatment.
Risks Fainting, dizziness, or nausea, due to hypotension. Paresthesias, bleeding, allergic reactions, excessive immune suppression, clotting of blood in the machine. Very rarely, deaths can occur.
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Risks of Plasmapheresis:

As with any medical procedure, plasmapheresis carries some risks. The following table summarizes the possible risks associated with plasmapheresis:

Risk

Description

Hypotension Patients may experience fainting, dizziness, or nausea due to low blood pressure during or after plasmapheresis
Paresthesias Tingling or numbness as a result of hypocalcemia can occur. It is treated with calcium supplementation.
Fatigue Some patients may experience fatigue after plasmapheresis, but it usually resolves within a day
Bleeding or Allergic Reaction Bleeding may occur because of the heparin or anticoagulant used in the tubings. Allergic reactions can also occur.
Immunosuppression Plasma exchange can temporarily suppress the immune system, increasing the risk of infection
Clotting It is possible that the blood clots in the tubing during the procedure 
Death Although very rare, deaths can occur due to infection, hypotension (shock), or allergic reactions.
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Conclusion

Plasmapheresis is a treatment option for several neurological conditions, including MS, NMO, and ADEM.

The efficacy of plasmapheresis varies depending on the underlying condition, but it is beneficial in many cases.

Plasmapheresis is a specialized medical procedure that requires specific equipment and trained personnel.

As with any medical procedure, it carries some risks, but these risks are generally considered to be low. Patients considering plasmapheresis should discuss the potential risks and benefits with their healthcare provider.

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What do you think?

Written by Dr. Ahmed

I am Dr. Ahmed (MBBS; FCPS Medicine), an Internist and a practicing physician. I am in the medical field for over fifteen years working in one of the busiest hospitals and writing medical posts for over 5 years.

I love my family, my profession, my blog, nature, hiking, and simple life. Read more about me, my family, and my qualifications

Here is a link to My Facebook Page. You can also contact me by email at contact@dibesity.com or at My Twitter Account
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