Multiple Sclerosis (MS)

At Irino CLINIC Inc., Dr. Takahiko Saida, Ph. D. provides the best and latest medical treatment for Multiple Sclerosis. (Appointment only)

About Multiple Sclerosis (MS)

There are the relapse period and the remission period with MS patients, and there was a time when it was believed that MS was not active during the remission period. However, with the utilization and progress of MRI, it became apparent that some new lesions were appearing even at the seemingly stable remission period. It has become clear that this so-called relapse was just a tip of the iceberg, and occurrences of new lesions in the brain with no symptoms were found at an average of 20 times more than that of relapses.

The biggest unsolved problem of MS is that after a certain period of time since the onset, although relapses become less noticeable, the changes sustaining and increasing impairment continue.
At present time, an effective medical treatment to contain the transition to the secondary progressive state, the continuing progression of impairment has not been found, so it is important to prevent the continuing progress of impairment from starting.
In order to achieve that, what we can do is to stop the activities of the disease completely by not allowing any further deterioration, and if possible, prompt the recovery to mitigate the impairment.

In the past, it was believed that the development of brain atrophy occurred only in patients with prolonged and severe MS. However, the recent study shows that the progression of brain atrophy is almost at a constant rate, regardless of types or stages of MS. In other words, the brain atrophy progresses at a constant rate, throughout the early state of MS, Relapsing-Remitting MS, until after its transition to secondary progressive MS. Dementia emerges only when progress of brain atrophy reaches to a certain level.

The characteristics of brain and spinal cord cells are highly complex and hardly regenerative, unlike most other organs’ cells like liver or skin, which have a certain regenerative ability. Therefore, it is imperative to prevent the death of nerve cells and the decrease of nerve fibers from the initial stage of MS.

NEDA-4 (No Evidence of Disease Activity) MS treatment concept is recognized internationally.

1. No relapses
2. No disability progression
3. No new or enlarging T2 lesions on MRI
4. No brain volume loss

At present, there are about twelve drugs available in the world,
and five of them are available in Japan (as of 2015)

The first-generation drugs

Low effectiveness is a common disadvantage.

Interferon (Betaferon, AVONEX): self-injection (every other day, once a week), Disadvantages: Initial fever and fatigue
Glatiramer acetate (COPAXONE): self-injection (everyday), Disadvantages: frequent injection and pain.
Approved recently in Japan, but an old drug in other countries.

The second-generation drugs

Highly effective.
Japanese doctors lack experiences with the drug and not aware that it can be administered safely.

Fingolimod (IMUSERA, GILENYA): Oral medication, one capsule per day.
Some patients may develop mild side effects on liver.
TYSABRI: Intravenous (IV) medication. The most effective medication.
Approved in Europe and US in 2004. Available in Japan since 2014.
As a side effect, Progressive Multifocal Leukoencephalopathy (PML) may develop in some cases, however the risk can be determined by a test in advance.
For 3% of patients, it becomes ineffective within 6 months – 1 year.
Most patients using the drug do not develop relapse, but may not be fully effective for a patient with progressive MS.

Other medicines

BG-12: Oral medication, completed the clinical trial in Japan.
Alemtuzumab (Campath): Intravenous (IV) for five days > no treatment for a year
> Intravenous (IV) for three days > no treatment for five years
Approved in US and Europe in 2013. The most effective.

To achieve NEDA-4, aggressive application of effective treatment from the very early stage of MS is imperative.

Unfortunately, according to the Japanese Society of Neurology guidelines for treatment of MS, effective second-generation drugs such as Natalizumab (TYSABRI) or Fingolimod (IMUSERA, GILENYA) are only to be administered after the first generation drug, Interferon is proven ineffective.

All the currently available MS medications including the second-generation drugs are most effective if used at the early stage of MS, and they can be safely administered to many patients from the early stage under the doctor’s proper guidance.

Neuromyelitis Optica Spectrum Disorder (NMOSD)

NMOSD is an inflammatory disease of the central nervous system that can affect the optic nerves, brain stem, spinal cord, and brain. It can be mistaken for multiple sclerosis, but accurate diagnosis is essential because some drugs used for multiple sclerosis can worsen NMOSD.

NMO (Neuromyelitis Optica Disorder) was believed to affect both the optic nerves and spinal cord. However, to some, only the optic nerve gets affected, while others only get the spinal cord affected. In recent findings, there are some get neither the optic nerves nor the spinal cord affected, but only the brain. Therefore, about half of the patients were not diagnosed as NMO. In order to differentiate, the unifying term Neuromyelitis Optica Spectrum Disorder (NMOSD) is now officially used.

NMOSD criteria are; anti-aquaporin antibody (AQP4) positive, and three or more long vertebral lesions in the spinal cord. If there is either condition, it can be diagnosed as NMOSD.
Plasma exchange or pulse therapy is effective if applied immediately after the acute deterioration. Especially, plasma exchange is definitely effective if performed in early stage. For example, a patient suddenly lose sight due to a severe relapse, if plasma exchange was started within 2-3 days, possibility of recovery is high. However, if two weeks or one month passed, there is a possibility of no recovery.

Therefore, the correct diagnosis is necessary, and if the patient is diagnosed with severe relapse, the effective plasma exchange or both the plasma exchange and pulse therapy should be applied immediately.
Also, relapse of NMOSD is obvious and tends to lead to impairment, however its progression rarely continues, prevention of relapse is the effective measures to prevent the impairment progression.

As a long-term medical treatment for prevention of relapse, administration of an existing immunosuppressive medication or a combination of those medications can prevent the relapse in the most of the patients.

High dose of steroid (such as predonine) is very effective for the prevention of relapse, however the occurrence of side effects is inevitable. Even though it is rarely necessary to administer steroid because of immunosuppressive medications, in many cases, only the steroid is administered for treatment, which results in side effects such as obesity, osteoporosis, bone fracture, hyperlipidemia, arteriosclerosis, diabetes, skin disorder, or infectious disease.

Anti-MOG antibody–positive disease

It has been drawing the international attention for a few years now, however it is no clear whether it is a unique disease or not. There is a disease called ADEM(acute disseminated encephalomyelitis）, which shows similar symptoms to MS, but only happens once and never relapses, and commonly found among children. It has been found that many of those affected children are anti-MOG antibody-positive.

Among the patients who have been diagnosed with neuromyelitis optica, there are those with repeated relapses of optic neuritis, and have seldom or no abnormality in brain MRI, and when anti-aquaporin-4 antibody was measured due to the suspicion of a NMO, the result is negative. There are some patients with anti-MOG antibody positive disease among them. Also, among the patients who have been diagnosed with MS, there are some patients with anti-MOG antibody positive disease.

With anti-MOG antibody positive disease, the patients experience the repetition of relapses, however, their recovery is relatively well. Steroid works very well, but its side effects are the problem. Plasma exchange also very effective.

There are very little patients with anti-MOG antibody positive disease in the world.
Its name has only been decided recently. Its course or how the patients will be in the long term have not been known yet. If you are diagnosed with NMO and your anti-aquaporin-4 antibody test result is negative, it is highly recommended to be tested whether you have anti-MOG antibody positive disease.