MGnet promoted its very first online presentation in October of 2000. Our guest speaker was Dr Florence Weijnen, a Dutch medical biologist, who shared with us the results of her recently published work on The Quantitative and Qualitative Evaluation of Bulbar Symptoms in Patients with Myasthenia Gravis.

This research brings a relevant contribution to the understanding of bulbar symptoms (facial weakness, difficulties in chewing, swallowing, articulation, breathing, and weakness of the neck muscles) in patients with generalized Myasthenia Gravis (MG). The aim of the study was to quantify this bulbar weakness.

A series of standardized, non-invasive measurements was developed to quantify the bulbar weakness. The procedure included evaluation of facial expression, masticatory muscle weakness and swallowing difficulties through a series of tests and equipment. A special statistical procedure was used to determine with which of the measurements optimal discrimination was achieved between patients with bulbar MG and subjects without bulbar weakness.

The results show that over 85% of the subjects can be classified correctly with three of the measures of facial expression, swallowing, and mastication. The lip-length index, which was used to determine the ability to smile, is a rapid, non-invasive measurement that does not require complex instrumentation. This measurement is of particular value to clinical practice. The analysis of the results showed that about 80% of the subjects could be classified correctly on the basis of only this measurement.

Dr. Weijnen ended her presentation by saying that the use of the measurements developed is not limited to patients with MG, but can also be used with other neuromuscular diseases.

It was extremely interesting and a unique opportunity to hear first-hand about the work of one of those who is working in the area of MG. A big Thank You to Dr. Florence Weijnen!

For more information about her research please see
Dr. Weijnen's website www.med.uu.nl/BTHK/res_myas.htm

The complete text follows.

Florence Weijnen, PH.D. -Medical Biologist -Department of Oral Maxillofacial Surgery, Prosthodontics and Special Dental Care -Faculty of Medicine of the Utrecht University in The Netherlands -recently published her thesis on The Quantitative and Qualitative Evaluation of Bulbar Symptoms in Patients with Myasthenia Gravis. A presentation of her research is followed by a question and answer session.

This log has been edited from its original version for your convenience.

KellyCarson: I would like to first welcome Dr Weijnen to our Membership meeting and thank her for taking the time to come. Welcome.

FlorenceW: Good Evening from Holland! Bulbar myasthenia gravis: quantitative and qualitative evaluation.

*Aim of my study
Bulbar symptoms of myasthenia gravis (MG) include facial weakness, difficulties in chewing, swallowing, articulation, and breathing, and weakness of the neck muscles. The aim of my study was to quantify this bulbar weakness. Patients with bulbar MG were compared to three other groups:

(1) a control group of healthy subjects
(2) patients with MG in remission who previously had bulbar symptoms (remission group)
(3) patients with ocular MG who never had bulbar symptoms (ocular MG group)

The latter two groups were included in the study to investigate whether any subclinical weakness may be observed in these patients (= bulbar symptoms that these persons and their neurologist are not aware of).

*Measurements
A series of standardized, non-invasive measurements was developed to quantify the bulbar weakness. The procedure included evaluation of facial expression, masticatory muscle weakness and swallowing difficulties.

*General results
In general, we only found significant weakness in the bulbar MG group. Only limited evidence was found for subclinical weakness in the remission group. No evidence was found in the ocular MG group.

*Vertical smile
Facial weakness may lead to a flat, expressionless face, with drooping of the mouth. Weakness of the lips can cause inability to whistle or eat from a spoon and may also cause a characteristic vertical smile. This facial weakness was quantified with the lip-length and snout indices, which are an indication of the degree to which a person is capable of smiling and pursing the lips. These indices were significantly smaller in patients with bulbar myasthenia gravis.

*Difficulties in swallowing and mastication
Difficulties in swallowing may cause choking and nasal regurgitation in patients with bulbar MG. Indeed, the duration of the swallowing process (measured with surface electromyography (EMG) recordings of the submental and swallowing muscle complexes) was increased in patients with bulbar MG. We also demonstrated tongue weakness with the use of a tongue force transducer. One could expect that patients with bulbar MG would try to avoid swallowing difficulties by prolonging the mastication of food. However, the number of chewing cycles that bulbar MG patients needed before swallowing was not increased. This lack of compensation may be due to masticatory muscle weakness. Indeed, the amount of masticatory muscle activity during each chewing cycle was decreased, as well as the maximal activity that could be produced by the masticatory muscles. Furthermore, experiments with artificial test food show that patients with bulbar MG chew less efficiently.

*Statistical analysis
We used a special statistical procedure to determine with which of our measurements optimal discrimination was achieved between patients with bulbar myasthenia gravis and subjects without bulbar weakness (including healthy controls, patients in remission, and patients with ocular myasthenia gravis). The results show that over 85% of the subjects can be classified correctly with three of our measures of facial expression, swallowing, and mastication. The lip-length index, which we used to determine the ability to smile, is a rapid, non-invasive measurement that does not require complex instrumentation. This measurement is particularly of value to clinical practice. Our analysis showed that about 80% of the subjects could be classified correctly on the basis of only this measurement.

*Questionnaires and interviews
Questionnaires and standard interviews were used to determine how bulbar weakness, if present, was experienced by the patients. The results show that some questions deserve special attention in clinical history taking if myasthenia gravis is suspected:

(1) A vertical smile was mainly reported by patients with low lip-length indices.
(2) A need to support the jaw during mastication was characteristic for patients with low bite force.
(3) A need to support the jaw to prevent it from opening was characteristic for patients with low masticatory muscle activity during mastication of test food.

*Portable setup
Finally, we developed a method for bedside quantification of bulbar weakness, which is based on our laboratory setup. This method includes equipment to evaluate facial expression, bite force, and tongue force in a short period of time (± 10 min). A comparison was made between patients with bulbar myasthenia gravis and healthy controls in both Pakistan and the Netherlands. Again, the patients with bulbar MG showed signs of muscle weakness. In addition, differences in bite force and tongue force between Pakistani and Dutch subjects were demonstrated.

*Summary
In summary, this study is an important step to a quantitative approach of bulbar weakness in patients with myasthenia gravis. Bulbar weakness was demonstrated in patients with bulbar myasthenia gravis. Their results were compared to those of patients with bulbar myasthenia gravis in remission, patients with ocular myasthenia gravis, and healthy subjects. Little evidence was found for subclinical weakness in the remission group, and no evidence was found in the ocular myasthenia gravis group. Further research is necessary to investigate the value of our experimental setup in longitudinal studies of bulbar function.

The use of our measurements is not limited to patients with myasthenia gravis, but can also be of value for patients with other neuromuscular diseases.
Thank you!

Q1: Is there a summary of all the symptoms of bulbar weakness?

The symptoms I described during the presentation are the main symptoms of bulbar weakness. Weakness of the neck muscles is also possible.

Q2: In cases of MG in remission or ocular MG...has the use of mestinon or prednisone been seen to make the cases worse and expand the symptoms?

I think that this type of question should be answered by a neurologist (I am a medical biologist.)

Q3: If patients have a decreased masticatory muscle activity, which is the consequence of this in pratical terms?

Masticatory muscle weakness results in difficulties to chew, especially on hard or tough food. In that case, people often change the type of food they eat.

Q4: How much do the characteristics of MG (progressive weakness) interfere with the process and the results of such a study?

The aim of the study was to quantify these symptoms. The measurements did not influence the symptoms.

Q5: In the process of diagnosing MG, which will be the contribution given by both the method and the equipment developed?

The measurements could be used during diagnosis of MG, especially the lip length index (measure of the ability to smile). However, the measurements will probably be used most to evaluate the symptoms over a longer period of time. To observe if the symptoms are improving or getting worse and to see if medication is working.

Q6: Your definition of bulbar MG seems to be like generalized MG. Is it the same?

Persons with bulbar myasthenia gravis may also have problems with other muscles (like arms or legs). This is indeed referred to as general myasthenia gravis.

Q7: Have any studies been done on quantifing ocular myasthenia symptoms?

I am not aware of studies on quantification of ocular MG symptoms. But this is really a different field of research, so I may have missed it. Up to now, there has been a lack of studies aimed at quantification of symptoms of myasthenia gravis.

Q8: How many patients were in each group?

There were 20 persons in each of the four groups.

Q9: Are the tools used for your measurements available to most neurologists?

Not all of them. The lip length index is performed with a sliding calliper or other measuring device, which everyone can buy easily.

Q10: I have breathing problems also with my MG and some bulbar symptoms -is this common?

Yes, breathing problems can also occur.

Q11: Is there an estimation of the percentage of MGers who are in remission from general MG but still suffer from bulbar MG?

Sorry, I don't know the answer to this question.

Q12: Are any pharmaceutical companies interested in using your methods for potential drug studies?

My thesis was only published a few weeks ago, and some of the individual papers are under review of medical journals. It will take some time before it will be possible to start pharmacological studies.

Q13: If you have bulbur MG but have arm and leg weakness then do have general mg or both general and bulbar?

In general, there are two types of MG: ocular and generalised mg. In generalised mg, a variaty of symptoms may occur: bulbar weakness, arm weakness, leg weakness, etcetera. In my study, I focussed on people with bulbar symptoms, who I described as having bulbar mg.