Ophthalmoplegia progressiva externa is a progressive and genetically determined paralysis of the extraocular muscles in the context of mitochondrial disease. The drooping of the eyelids is considered the main symptom, but cardiac arrhythmias can also occur. A causal therapy does not exist.
What is external progressive ophthalmoplegia?
Isolated paralysis of the inner or outer eye muscles is summarized under the clinical term “ophthalmoplegia”. Chronic progressive ophthalmoplegia is progressive paralysis of the extraocular muscles that occurs as a result of mitochondrial dysfunction. The extraocular muscles realize all rotations of the eyeball. The external eye muscles include the superior rectus muscle, the lateral rectus muscle, the inferior rectus muscle, the medial rectus muscle, the superior oblique muscle and the inferior oblique muscle. See usvsukenglish for What does the abbreviation BCS stand for.
These muscles receive their motor innervation from the III., IV. and VI. cranial nerve. In ophthalmoplegia progressiva externa, the paralysis of these nerves is caused by a genetic mitochondrial disease. A special form of this disease is ophthalmoplegia plus, which is associated with additional symptoms. There is a smooth transition between the plus form and the Kearns-Sayre syndrome.
The skeletal muscles rely on aerobic energy production. The term mitochondriopathy corresponds to neuromuscular syndromes that are associated with a dysfunction in the mitochondrial respiratory chain and thus problems in aerobic energy production. Such a phenomenon also occurs in chronic progressive ophthalmoplegia. In this case, the disorder affects the outer ocular muscles and is usually caused by deletions or point mutations at position 3243 in the mitochondrial DNA.
Multiple defects in this structure cause mitochondrial respiratory chain defects. In half of all cases, the special form of ophthalmoplegia plus is a sporadic genetic disease with singular mtDNA deletions and somewhat more rarely with mtDNA duplications. A maternally inherited point mutation in mitochondrial DNA can also be the cause. Often this mutation corresponds to mutation A3243G. In the context of nuclear modified genetic material, autosomal dominant and, more rarely, autosomal recessive cases can be present.
Symptoms, Ailments & Signs
Ophthalmoplegia progressiva externa can break out at any age. The main clinical sign is a drooping of one or both eyelids. In this context we are talking about ptosis. This key symptom is sometimes accompanied by massive restrictions in the movement of the eyes. As a rule, the symptoms are bilateral, but monolateral manifestations cannot be ruled out. In the case of bilateral eye muscle paralysis, there are often no characteristic double images.
As long as the paralysis in both eyes is approximately symmetrical, no squinting behavior can be observed. In contrast to central gaze palsy, the ophthalmoplegia progressiva externa has the oculomotor functions of the brainstem completely intact. Due to the severe paralysis, however, the intact structures can also show delayed movements. With ophthalmoplegia plus, for example, there are also muscle weaknesses in the extremities close to the body, on the face or in the swallowing muscles.
Cardiac conduction disorders and endocrinopathies with diabetes mellitus, delayed puberty or short stature are just as conceivable as axonal polyneuropathies, dementia, sensorineural hearing loss, pigment retinopathies or ataxia.
Diagnosis & course of disease
Methods such as creatine kinase, lactate dehydrogenase, resting lactate and serum pyruvate are generally recommended for the diagnosis of mitochondrial diseases. A neurological examination of the patient using ergometry or electromyography excludes an increase in lactate. Muscle biopsies and molecular genetic diagnostics can follow.
The thyroid hormone status and the thyroid antibody status are important diagnostic tools, especially for ophthalmoplegia progressiva externa. The doctor will probably make the suspected diagnosis based on the characteristic signs of the disease and the medical history. Myasthenia, gaze paralysis of other causes, oculomotor nerve palsy and brainstem lesions should be considered in the differential diagnosis. Senile ptosis and fibrosis syndrome must also be ruled out. In addition to the MRT, the means for this are the EMG, the ENG and the EKG.
The EMG shows decreased muscle activity. The ENG illustrates the reduced nerve conduction velocity and the ECG may show cardiac arrhythmias. The earlier the disease breaks out, the more unfavorable the prognosis usually is.
While the main symptom of ophthalmoplegia progressiva externa is ptosis, ophthalmoplegia plus other organs can be involved and this can lead to serious complications. Ptosis is the drooping of one or both eyelids. If this is not treated, the cornea of the eyes can dry out due to poor lid closure.
In addition to ptosis, ophthalmoplegia plus is also characterized by muscle weakness in the extremities, face and swallowing muscles. In addition to swallowing disorders, cardiac arrhythmias, various hormone disorders and delayed puberty can also occur. If cardiac arrhythmias are left untreated, the heart will be damaged in the long term. Difficulty breathing and severe heart failure may occur.
The complications caused by persistent cardiac arrhythmias can only be prevented by inserting a pacemaker. In severe cases, the heart can be so badly damaged that a heart transplant is necessary. The hormonal imbalances manifest themselves mainly in the form of diabetes mellitus, short stature or delayed puberty.
In the long term, untreated diabetes leads to cardiovascular diseases with the risk of heart attacks or strokes, polyneuropathies and a gradual decrease in physical performance. Another complication of ophthalmoplegia progressiva externa, but especially ophthalmoplegia plus, is the occurrence of dementia and disturbances in the coordination of movements.
However, the course of ophthalmoplegia progressiva externa depends on the time at which the disease began. The earlier it begins, the more severe the complications that arise.
When should you go to the doctor?
In the case of all diseases affecting the eyes with inflammatory symptoms or symptoms that limit vision, it is advisable to see a doctor. Eye sensitivity and possible vision loss are good reasons to see a doctor. If external progressive ophthalmoplegia is suspected, the first symptoms are unmistakable indications of a more serious disease.
Chronic progressive ophthalmoplegia is generally more severe when it occurs early in life. Children and young people should therefore see a doctor immediately if they experience symptoms such as restricted eye movement or a suddenly drooping eyelid. In many cases both eyes are affected by ophthalmoplegia progressiva externa, in others only one eye.
A visit to the doctor is advisable because ophthalmoplegia progressiva externa can have consequences that require treatment. These are very diverse. They can also affect other body regions, organs or organ functions. In many cases, surgical treatment of the drooping eyelid is advisable. This at least prevents the cornea from drying out due to poor eyelid closure. However, ophthalmoplegia progressiva externa cannot be cured.
Serious disorders of the endocrine glands and the conduction of impulses in the heart can occur in addition to the side effects that require treatment. Both lead to other illnesses. Ophthalmoplegia progressiva externa can lead to diabetes, polyneuropathy or dementia.
Treatment & Therapy
So far there is no causal therapy for the treatment of the genetic disease ophthalmoplegia progressiva externa and its special form ophthalmoplegia plus. For this reason, the disease is considered incurable and is only treated symptomatically and supportively. The symptomatic treatment usually corresponds to the administration of high-dose coenzymes Q10, which are also known as ubiquinone.
Substitution with carnitine or creatine is also one of the general treatment recommendations for mitochondriopathies. In this way, the muscular symptoms can be improved, especially in the plus form of the disease. Further treatment depends on the prevailing symptoms. Symptoms such as sensorineural hearing loss can be counteracted with implanted hearing aids, for example. If there are persistent cardiac arrhythmias in addition to the eye problems, the use of a pacemaker is indicated.
Heart transplantation is an option for the definitive resolution of progressive cardiomyopathy. To improve atactic phenomena and muscle weakness of the extremities, the patient can follow physiotherapeutic measures and, if necessary, strengthen the affected muscles. If diabetes is also present, an appropriate diet is recommended. In this case, the patient must also be supplied with insulin.
The care of the parents by a psychotherapist can be considered as a supportive measure. The patient himself may also benefit from psychotherapy or the exchange with other affected people, as can take place in a supportive help group.
Outlook & Forecast
The condition called ophthalmoplegia progressiva externa is an eye-related paralysis of at least one eyelid. Chronic progressive external ophthalmoplegia (CPEO) is mostly inherited. Over the years, increasing paralysis of the outer eye muscles and the eyelid muscle.
The visible consequences of ophthalmoplegia progressiva externa can be reduced surgically. However, ophthalmoplegia progressiva externa cannot be cured. Current studies are trying to improve the mitochondrial dynamics in selected subjects. The surgical procedures are proven because the affected eye cannot be completely closed due to the paralysis. A so-called exposure keratopathy could therefore develop in the long term due to drying out of the cornea.
Additional complaints only occur if the so-called Ophtalmophlegia Plus is present. This variant of ophthalmophlegia is characterized by other physical symptoms in addition to the typical droopy eyelid. For example, the muscles in the face, extremities or the swallowing system can be weakened. In the presence of cardiac arrhythmia, a pacemaker can now be used. Double vision can be corrected with prism glasses or surgically.
Although modern medicine can treat many of the accompanying symptoms of ophthalmoplegia plus, the prognosis for this variant of ophthalmoplegia is not as good. The prerequisite for a persistently low-symptom condition is that the therapeutic approaches pursued are effective.
The reasons for the disease-causing gene mutation have not yet been finally clarified. For this reason, ophthalmoplegia progressiva externa has not yet been actively prevented.
Since ophthalmoplegia progressiva externa is a genetic disease, it cannot usually be completely cured. For this reason, only a few and usually only very limited aftercare measures are available to those affected. First and foremost, the affected person should consult a doctor at an early stage in order to prevent the occurrence of further complications and symptoms.
Usually, self-healing cannot take place. If the person concerned or the parents wish to have children, a genetic examination and counseling should always be carried out in order to prevent a recurrence of ophthalmoplegia progressiva externa. Those affected are dependent on regular checks of the internal organs with the disease, whereby the heart should be checked in particular.
In general, very strenuous or stressful activities should be avoided in order not to put unnecessary strain on the heart. It is also necessary to take various medications, whereby the person concerned should always ensure that the dosage is correct and that it is taken regularly. Many patients also depend on psychological support from their own families. The disease may result in a reduced life expectancy for those affected.
You can do that yourself
Since ophthalmoplegia progressiva externa is a genetic disease, there are few opportunities for self-help. However, although there is no causal therapy, measures accompanying medical treatment can and should be carried out.
Doctors and physiotherapists provide instructions for exercises that can be carried out independently at home. This makes it possible to strengthen the muscles weakened by the disease and to improve the patient’s body awareness. It is important to do these exercises continuously, as this is the only way to improve performance.
In addition to physiological accompanying measures, psychological offers can help to deal with the effects of the disease. The support provided by a psychotherapist can benefit both patients and parents and relatives. The therapists can learn self-help measures in order to reduce the stress experienced as a result of ophthalmoplegia progressiva externa.
Since such an illness represents an extreme situation for a family, value should be placed on balancing activities. Physical activity, if possible in the fresh air, can prevent depression and improve the quality of life. The social environment of the sick person and their family should not be neglected either. An intact social network can help to deal with the effects of the disease and to find new courage to face life.