Multiple sclerosis – Neurology

MS is a chronic inflammatory disease of the central nervous system (ie brain and myelum). At different times, this inflammation disrupts the function of nerve tracts in the brain, myelum or optic nerve, causing neurological complaints and symptoms. The occurrence of new complaints or the worsening of existing complaints, is called a relapse.

Because the inflammation might occur everywhere in the central nervous system, the symptoms vary a lot:

The following complaints occur quite frequently:

Impaired vision of 1 eye
Double vision
Sensory complaints (tingling – numbness)
Paresis of arm/leg
Impaired balance and/or coordination
Memory difficulties
Fatigue
Impaired bladder function

The severeness of the disease, varies between patients, depending on location of inflammatory lesions, the frequency of relapses, the age of disease onset and the response to treatment.

Based on the evolution of complaints in time, 3 forms of MS are described. There is no specific test to determine the differences among these forms.

The most common form is ‘relapsing remitting MS’ (RRMS), showing relapses followed by remission (ie complete or incomplete recovery).
After several years, a certain number of patients with RRMS evolve to ‘secondary progressive MS’, showing progressive worsening, independently of relapses.
‘primary progressive MS’ is a rare form, showing progressive worsening, without relapses.

The cause of MS is not truly known at this moment but the development of the disease is probably based on an interaction between a genetic predisposition combined with certain environmental factors such as infection, low vitamin D, lack of sun exposure ….

The diagnosis of MS is based on the patient’s story, the neurological exam and the results of investigations:

Analysis of blood samples and a lung X-ray to exclude other inflammatory diseases
MRI scan of the brain and spine
Evoked potentials ie a functional examination of certain nerve tracts (sensory tract, vision and auditory tract).
A lumbar puncture

MS can not be cured, but many drugs are available to modify the disease.

To treat a relapse, cortisone is administered intravenously or sometimes orally during 3 to 5 days.

After diagnosis, a drug modifying therapy (DMT) is usually started to suppress:

The occurrence of new relapses
The occurrence of new inflammatory lesions on MRI
The long term consequences of the disease (disability)

Among the treatments of RRMS we currently talk about:

1st line treatments: usually started after diagnosis.

Interferons:
- These drugs modulate the immune system. The exact mode of action is not truly elucidated
- These drugs need to be injected, usually through a device:
  - Rebif^®: 3 times a week
  - Avonex^®: once a week
  - Plegridy^®: once every 2 weeks
  - Betaferon^®: every 2 days
- The cost without reimbursement is about 600 – 700€ / month
- These drugs are generally safe but the liver function needs to be checked from time to time and sometimes a depressive mood might get worse. All interferons cause flew like symptoms, mainly on the day of injection.
- These drugs can be used during pregnancy.
Glatiramate acetate (Copaxone^®):
- Also an immune modulatory drug
- Injected daily or 3 times a week
- Cost without reimbursement is about 700€ / month
- This drug is usually very well tolerated and can be used during pregnancy.
Dimethyl fumarate (Tecfidera^®):
- This drug has an anti-inflammatory and immune modulating mode of action
- It’s a tablet bid (one in the morning and one in the evening)
- Cost without reimbursement is about 850€ / month
- Gastro intestinal complaints and especially flushing might occur as a side effect. Sometimes the white blood cell count drops, implying a risk for PML (progressive multifocal leukencefalopathy – see natalizumab).
- Pregnancy should be avoided, although based on current data the drug seems to be safe for the fetus.
Teriflunomide (Aubagio^®):
- This is also an immune modulating drug
- It’s a tablet to be taken once a day
- Cost without reimbursement is about 800€ / month
- This drug might cause gastro intestinal complaints, hair thinning, headache and impaired liver function (the first 6 months the liver function needs to be checked frequently with a blood sample).
- Pregnancy should be avoided
Ozanimod (zeposia®)
- Like fingolimod, ozanimod makes inflammatory cells collect in the lymph nodes, so eventually less inflammatory cells reach the central nervous system and MS activity is suppressed
- It’s a tablet to be taken once a day
- The cost without reimbursement is about 1250€/month
- When the tablet is started, the heart rhythm might drop a bit. That’s why a cardiogram is checked first and the dose is build up during the first week. Rarely the heart rhythm needs to be controlled during a few hours
- The first months the liver function needs to be checked regularly, some infections might occur more frequently and for some patients a control of the retina (eye) is mandatory. So far 1 case of PML described among patients taking ozanimod
- Pregnancy needs to be avoided
Fingolimod (Gilenya^®):
- Fingolimod blocks a certain receptor on inflammatory cells, keeping them mainly in lymph nodes. Less inflammatory cells are circling around in the blood and eventually moving to the central nervous system suppressing the inflammatory disease activity.
- It’s a tablet to be taken once a day
- The cost without reimbursement is about 1700€ / month
- The first dose needs to be taken in the hospital, because the heart rhythm might drop. Certain infections such as shingles or genital warts occur more frequently and 3 months after initiation of therapy, the retina needs to be checked by the ophthalmologist. Certain skin tumors also might occur more frequently as does PML (see natalizumab).
- Pregnancy needs to be avoided
ponesimod (Ponvory®)
- Like fingolimod, ozanimod and siponimod, ponesimod makes inflammatory cells collect in the lymph nodes, so eventually less inflammatory cells reach the central nervous system and MS activity is suppressed
- It’s a tablet to be taken once a day
- The cost without reimbursement is about 855€/month
- When the tablet is started, the heart rhythm might drop a bit. That’s why a cardiogram is checked first and the dose is build up during 2 weeks. Rarely the heart rhythm needs to be controlled during a few hours. The first months the liver function needs to be checked regularly, some infections might occur more frequently and for some patients a control of the retina (eye) is mandatory.
- Pregnancy needs to be avoided

2^nd line treatments: used in case of a very active disease on the moment of diagnosis or mostly used in case of failure of a 1^st line treatment (failure = new relapses and/or new laesions on MRI and/or progression).

Cladribine (Mavenclad^®)
- This drug slowly destroys B and T lymphocytes (= inflammatory cells). Thereafter the bone marrow produces new lymphocytes which are less oriented against the central nervous system. Cladribine Is called an immune reconstitution therapy. .
- It’s a tablet to be taken during 2 weeks (with a 4 weeks interval) in the first and second year. Ideally, afterwards no other DMT is needed anymore.
- Cost without reimbursement is at least 10000€.
- This drug is generally well tolerated. Shingels might occur more frequently.
- Pregnancy needs to be avoided during this therapy and is only allowed 6 months after the last dose. Also male patients can not conceive a child during therapy.
Natalizumab (Tysabri^®):
- Natalizumab is a monoclonal antibody that prevents the migration of white blood cells (inflammatory cells) to the central nervous system, reducing inflammatory disease activity
- this drug is administered by infusion or by subcutaneous injection every 4 to 6 weeks.
- Cost without reimbursement is about 1600€ /infusion
- This drug is generaly well tolerated. There is a risk of activation of the JC virus. Many people carry this virus in their body without symptoms. In case of a reduced immunity, this virus can be activated and cause an infection in the brain (PML or progressive multifocal leukencephalopathy). The risk of this infection depends on the duration of treatment with the drug and the level of antibodies.
- Pregnancy should be avoided, however the drug seems to be relatively safe. Sometimes natalizumab is continued during the 1^st and 2^nd trimester of the pregnancy.
Ocrelizumab (Ocrevus^®)
- This is also a monoclonal antibody that binds to CD20 B lymphocytes breaking down these cells. The loss of these B lymphocytes reduces the inflammatory disease activity.
- This is also an infused drug, every 6 months.
- Cost without reimbursement is about 10000 € /infusion
- During the infusion, rash, itching, low blood pressure, headache, flew like symptoms, … might occur. Usually these symptoms can be mitigated by reducing the speed of infusion.
- Pregnancy should be avoided.
- Ocrelizumab is also the only drug approved for PPMS
Ofatumumab (Kesimpta ®)
- This is also a monoclonal antibody that binds to CD20 B lymphocytes breaking down these cells. The loss of these B lymphocytes reduces the inflammatory disease activity.
- This drug is injected by an auto injector at home, once a month
- Cost without reimbursement is about 1700 € /injection
- This drug is well tolerated. Irritation might occur at the site of injection
- Pregnancy should be avoided.
Alemtuzamab (Lemtrada^®)
- This is also a monoclonal antibody binding CD52 cells (certain T and B lymphocytes). The drug causes a rapid death of these cells. Thereafter the bone marrow produces new lymphocytes which are less oriented against the central nervous system. Alemtuzamab is also an immune reconstitution therapy (just like cladribine)
- The drug is administered by infusion during 5 days and 1 year later during 3 days. Ideally, afterwards no other DMT is needed anymore.
- Cost without reimbursement is about 7000€/infusion day
- Sometimes Lemtrada is considered as a third line drug. It’s an effective drug, but there are side effects to consider:
  - During the infusion, rash, headache, fever, itching and nausea might occur.
  - Rarely hemorrhages in the lungs or in the brain might occur, or damage to cervical arteries.
  - The risk of an infection with herpes zoster (shingles) is elevated
  - The major concern is the occurrence of auto immune disease. 1 in 3 patients develops thyroid dysfunction. Other, luckily rare findings are low platelets (TTP) or inflammation of the kidneys or liver. To screen for these possible auto immune phenomena, blood and urine samples need to be checked every month during 4 years after the last infusion.
- Pregnancy should be avoided.

Attention

Continuously new drugs for MS are explored and developed. Recently, the following drugs became available in Belgium: siponimod (Mayzent^®) for active SPMS, ozanimod (Zeposia^®), ofatumuab (Kesimpta^®) and ponesimod (Ponvory^®) for RRMS.

Siponimod (Mayzent^®) is available for SPMS. The mode of action is similar to fingolimod, ozanimod and ponesimod. It's a once daily oral drug.

For the treatment of PPMS only ocrelizumab is approved.

Very often other drugs are prescribed to control symptoms of fatigue, spasticity, bladder dysfunction, ...

Usually physiotherapy is an important part of the therapy.

TMST or transmural MS team

To improve the care of MS patienst, the TMST is organized in collaboration with the NMSC (national MS center of Melsbroek – near Brussels). This multidisciplinary consultation takes place on Monday afternoon in the Sint-Jozefs hospital in Mortsel (Molenstraat 19 2640 Mortsel). Every patient is seen by the following care givers:

The GZA neurologist
A physical doctor (GZA)
A NMSC nurse
A NMSC physiotherapist
A NMSC dietrician
A NMSC social worker.

Every care giver takes 30 minutes to evaluate and listen tot he patient. So the whole consultation takes 3 houres. Afterwards the patients file and situation are discussed to provide advices or certain care programs in the NMSC.

The cost of this consultation is only 1.80 €.

A few times a year we have a multidisciplinary MS consultation, where you can visit a social worker of the MS-liga

Dr. Debruyne and dr. Verstappen are the MS-experts of the GZA department of neurology.

From june 2021 on, MS patients can take advantage of free psychological care. This service can be applied for by the treating GZA neurologist.