Myasthenia is a long-term disease. However, in 90 % of the patients it is possible to reach the improvement of the patients` state or even erasing all the clinical symptoms.

 

 It all started in year 1934 when Scottish physician Ms. Mary Walker administered the substance called prostigmine to the patient who suffered with a severe form of myasthenia gravis. The result was however short but undoubted improvement of the muscles` weakness.

Medicines of the same kind are now called „acetylcholine inhibitors“. Acetylcholinesterase is the enzyme, chemically the protein molecule that disintegrates (hydrolises) the acetylcholine in two non-effective substances. By slowing down the decomposition, there remains more of this compound left in the synaptic junction and this leads to improvement of neuro-muscular transition. We would like to emphasize these medicines do not treat the disease directly, however are necessary in lighter forms of myasthenia gravis where the state of the patient does not worsen.

The medicines of first choice in the Czech Republic are Mestinon (pyridostigimine) or Mytelase (ambenonium), occasionally use Ubretid (distigmine) or Syntostigmin (neostigmine). These are to be administered individually, according to the neurologist who treats the patient. According to the patients` daily activities, both Mestinon and Mytelase are to be taken 3 – 5 times a day. If taken on empty stomach, this results in faster absorption, especially in patients who suffer from weakness of the oral muscles in the morning. The side effects of these drugs include muscle spasms resulting into the fingers spinning, diarrhoea, salivation and increased lacrimation. Overdosing or misusing of acetylcholinase inhibitors may result in so called cholinergic crisis.

If any of these side effects occur, please do contact your neurologist promptly and lowering of the dosages may be advised to you then.

 

Drugs affecting immune system

 Corticosteroids (corticoids) lower the inflammation activity of leucocytes and the production of antibodies. They are used for treatment of patients together with using ACHE inhibitors. These substances are represented by drugs called Prednisone and Medrol.  In one third of patients, especially those who suffer of problems with biting, swallowing and articulation, corticosteroids can severely worsen the state of such patients. Therefore it is crucial to raise the dosages to approx. 1mg/kg of patient´s weight. The approximate length of administration of these drugs is from six to eight weeks and then the dosages are lowered down slowly, until the sustaining level is reached. The treatment cannot be stopped suddenly, but very slowly with lowering the dosages otherwise this may result into worsening the disease and symptoms!!! The end of the treatment is suggested to be consulted with the specialist.

Corticosteroids have many side effects. For instance they increase degradation of proteins, increased elimination of potassium, osteoporosis, ulcers, increasing of cholesterol level in blood etc. Especially within the older men there might be a risk of steroid myopathy which can be demonstrated by muscle weakness in thigh muscles (see the article). Therefore patients are usually undergoing preventive treatment with potassium and medicines that protect the gastric mucose. Patients with higher risk are observed for the density of bones or calcium in various forms is administered.

Immunosuppressive therapy is usually started when there is a need of the increase of corticosteroids´ effect. The most used drug from this group of medicines is azathioprine (Azaprine, Imuran registred in the Czech Republic). There is a need of observing the levels of proteins and to perform the liver tests. If the symptoms are still lasting or repeating, more efficient drugs are administered to the patients. For inst ance these are Cyclosporine A (Equoral, Sandimun, CellCept – mycophenolate mofetil), Methotrexat or Prograf (tacrolimus, FK 506).

In very rare cases, the patient needs to undergo the treatment known as plasma exchange, (occasionaly imunoadsorption. This is mechanical process when plasma is cleaned from antibodies that cause the problem to the patient. Another option is to administer intravenous infusions of human immunoglobuline known as IVIG (Flebogamma, Endobulin, and Kiovig). This very expensive but also effective treatment is used in patients, when the disease is progressing very quickly or when patient falls into state called myasthenic crisis. Exceptionally can be this process repeated approx. once in one to three months, mostly in cases when the patient is not sensitive to neither the corticosteroid nor immunosuppressive treatment or the severe side effects of the treatment are not easy to co-ordinate.

 

Experimental treatment 

There are medicines that are in the research at the moment. Currently, the most promising can be the monoclonal antibodies (for instance Rituximab), high dosages of cyclophosphamide together with administration of the growth factor. Also “antisense therapy” (Monarsen EN 101) is recognised as the "latest fashion” in treatment of myasthenia gravis.

 

Thymectomy – surgical removal of the thymus gland

We suggest thymectomy to some patients as the treatment of their state. Patients are scheduled for the surgery at the thoracic surgeons. The discussed subject has been the type of thymectomy that patient should undergo. As to our experience, the only method how to eliminate whole thymus is thymectomy with the need of cut through the sternum. Then whole thymus is removed completely. The gland is in the shape of the butterfly that is attached to the trachea and wrapped around. It was proved this surgery is mostly effective within younger patients (until 55-60 years) when thymus can undergo many infective stages. The complete effect of thymectomy with giving up all the patient´s  medicines is usually reached after two years of the surgery. Only patients who are in clinical remission of the disease (i.e. with no symptoms of myasthenia) are suggested for thymectomy. The complications after the surgery are none, the recovery is very fast. Moreover, if the surgery is not provided on time, the risk of the severe progress of the disease is very high and this may lead to the irreversible status with long-term connection of the patient to the breathing apparatus!!! .

Following reason of performing the thymectomy may be the appearance of the thymoma, mostly benign tumour on thymus. It occurs mostly around the age of 40. Every removed thymus undergoes the histological check and then further treatment can be decided.

More information about thymectomy can be found at these pages:

here, here and here

Myasthenia gravis and thymectomy:

Treating scars or this page

 

Long-term treatment

 The long-term treatment is suggested to the patients who are not advised for the surgical removal of the thymus. Also, there may be patients who have to follow on with their treatment even after the thymectomy. The treatment varies according to every patient´s needs. It is very individual whether the patient will keep using only one kind of medicine or combination of more. Usually, when there is progress of the disease, patient´s medicines or combination of them may be raised, or also lowered, all according to his/her state.

 

Acute states´ treatment

There may be plenty of effects that may result into severe worsening of patient´s state. What may cause this sudden change? Infectious disease, medicines that worsen the state of the patient, emotional stress, surgery, etc. may lead into the situation when patient needs to be connected to the lung ventilator. Patient may notice himself/herself when the swallowing, biting, articulation or breathing gets worse. Myasthenic crisis looks very similar to cholinergic crisis that can be seen at the patients who overdose themselves with ACHE inhibitors. Cholinergic crisis differs from myasthenic crisis by extreme expectoration, myosis apart from same symptoms as myasthenic crisis – muscle weakness and lung failure. In both cases please do contact ER telephone line

As to the treatment, usually series of plasma exchange (4 to 7 every other day) or intravenous infusion of human imunoglobulines are performed. Not only fast recovery follows such treatment, but also plenty of complications may result, such as pneumonia, homeostasis disruption, etc. The treatment must be provided by special medical team.

 

 Dangerous medicines

Not all the medicines that myasthenic patient might get prescribed by physician are safe for him/her. Some of the medicines may worsen the disease or even start the disease. The medicines that´s therapy may result into myasthenia gravis are especially penicilamine, interferon alfa and sometimes, in very unique cases, myasthenia may occur in patients who undergo bone medulla transplant. Not all the physicians are aware of dangerous medicines and myasthenia gravis; therefore we suggest the patient to consult the prescribed or OTC medicines with their neurologist – specialist before taking them.

The dangerous medicines´ list is in the section for professionals on these pages.

Especially dangerous are medicines belonging to the antibiotics such as: tetracycline, gentamycine, chloramphenicole, erythromycine, tobramycine, kanamycine, klindamycine, doxycycline, ofloxacine and chinolones. Cefalosporines are the safe treatment for myasthenic patients.

Another group of dangerous medicines are central and peripheral myorelaxants, anaesthetics, anxiolytics and neuroleptics.

Corticosteroids (Prednisone, Medrol, and SoluMedrol) are standing beside dangerous drugs because we treat myasthenia with these; on the other hand, in group of 20 percent of patients they may cause myasthenic crisis when the treatment is stopped too soon. Even using of ointments, creams, sprays – local forms of drug administration may result into myasthenic crisis.

Every myasthenic patient is an individual and his/her treatment must be considered individually. Especially when treating additional diseases. For instance, when treating hypertension, epilepsy, hypercholesterolemia etc. It is always necessary to consider the benefit and risk for the patient him/herself.

 

Thank you for the translation Veronica