Ophthalmoplegia progressiva externa is a progressive and genetic paralysis of the external eye muscles in the setting of mitochondriopathy. Drooping of the eyelids is considered the leading symptom, but cardiac arrhythmias may also occur. No causal therapy exists.
What is ophthalmoplegia progressiva externa?
The clinical term “ophthalmoplegia” refers to isolated paralysis of the internal or external eye muscles. Chronic progressive ophthalmoplegia is a progressive paralysis of the external eye muscles that occurs as a result of mitochondrial dysfunction. The external eye 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. These muscles receive their motor innervation from the IIIrd, IVth and VIth cranial nerves. In ophthalmoplegia progressiva externa, the paralysis of these nerves is due to a genetic mitochondriopathy. A special form of this disease is ophthalmoplegia plus, which is associated with additional symptoms. There is smooth transition between the plus form and Kearns-Sayre syndrome.
Causes
Skeletal muscle relies on aerobic energy production. The term mitochondriopathy corresponds to neuromuscular syndromes associated with dysfunction in the mitochondrial respiratory chain and thus problems in aerobic energy production. Such a phenomenon is also present in chronic progressive ophthalmoplegia. The disorder in this case affects the external eye muscles and is usually caused by deletions or point mutations at position 3243 in mitochondrial DNA. Multiple defects in this structure cause mitochondrial respiratory chain defects. The special form ophthalmoplegia plus is a sporadic genetic disorder with singular mtDNA deletions in half of all cases and somewhat less frequently with mtDNA duplications. A maternally inherited point mutation of mitochondrial DNA may also be the cause. Often, this mutation corresponds to the A3243G mutation. In the setting of nuclear altered genetic material, autosomal dominant and, less commonly, autosomal recessive cases may be present.
Symptoms, complaints, and signs
Ophthalmoplegia progressiva externa can have onset at any age. The clinically central sign is drooping of one or both eyelids. In this context it is called ptosis. Sometimes this leading symptom is accompanied by massive movement restrictions of the eyes. As a rule, the symptoms are bilateral, but monolateral manifestations are not excluded. In bilateral ocular muscle paralyses, there are often no characteristic double images. As long as the paralysis is approximately symmetrical in both eyes, no strabismus is observed. Unlike central gaze paralysis, ophthalmoplegia progressiva externa leaves oculomotor brainstem functions completely intact. However, due to the severe paralysis, even the uninjured structures may show delayed movements. For example, in ophthalmoplegia plus, there is additional muscle weakness of the extremities near the body, on the face, or of the swallowing muscles. Cardiac conduction disorders and endocrinopathies with diabetes mellitus, delayed puberty, or short stature are also conceivable, as are axonal polyneuropathies, dementias, sensorineural hearing loss, pigmentary retinopathies, or ataxias show.
Diagnosis and disease progression
Methods such as creatine kinase, lactate dehydrogenase, resting lactate, and serum pyruvate are generally recommended for diagnosis of mitochondrial disease. Neurological examination of the patient is performed via ergometry or electromyography to rule out lactate elevation. Muscle biopsies and molecular genetic diagnostics may follow. Thyroid hormone status and thyroid antibody status are important diagnostic tools especially for ophthalmoplegia progressiva externa. The physician will probably already make the tentative diagnosis on the basis of the characteristic signs of the disease and the medical history. Differentially, myasthenias, gaze paralysis of other causes, oculomotor palsy, and brainstem lesions should be considered. Senile ptosis and fibrosis syndrome must also be excluded.The means for this, in addition to the MRI, are the EMG, the ENG and the ECG. The EMG shows decreased muscle activity. The ENG illustrates decreased nerve conduction velocity and the ECG may show cardiac arrhythmias. The earlier the onset of the disease, the less favorable the prognosis usually is.
Complications
While the leading symptom of ophthalmoplegia progressiva externa is ptosis, other organs may be involved in ophthalmoplegia plus, sometimes resulting in serious complications. Ptosis refers to drooping of one or both eyelids. If this is not treated, the cornea of the eyes can dry out due to poor eyelid closure. In addition to ptosis, ophthalmoplegia plus is also characterized by muscle weakness in the extremities, face and swallowing muscles. In addition to dysphagia, cardiac arrhythmias, multiple hormonal imbalances, and delayed puberty may also occur. If left untreated, cardiac arrhythmias cause long-term damage to the heart. Respiratory problems and severe heart failure may occur. The complications caused by persistent arrhythmias can only be prevented with the insertion of a pacemaker. In severe cases, the heart can be so badly damaged that even a heart transplant becomes necessary. The hormonal disorders manifest themselves mainly in the form of diabetes mellitus, short stature or delayed puberty. Untreated diabetes leads in the long term to cardiovascular diseases with the risk of heart attacks or strokes, polyneuropathies and gradual decrease in physical performance. Another complication of ophthalmoplegia progressiva externa, but especially of ophthalmoplegia plus, is the onset of dementia and disturbances in motor coordination. However, the course of ophthalmoplegia progressiva externa depends on the time of onset of the disease. The earlier it begins, the more severe the complications that occur.
When should you see a doctor?
A visit to the doctor is generally advisable for all diseases affecting the eyes with inflammatory symptoms or symptoms that limit the ability to see. Sensitivity of the eyes and possible loss of vision are good reasons to see a doctor. If ophthalmoplegia progressiva externa is suspected, the first symptoms are unmistakable clues to a more serious disease. Chronic progressive ophthalmoplegia is generally more severe when it occurs early in life. Therefore, children and young people should be presented to a physician immediately if they experience symptoms such as restricted eye movement or a sudden 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 lead to secondary symptoms that require treatment. These are very diverse. They can also affect other regions of the body, organs or organ functions. In many cases, surgical treatment of the drooping eyelid is advised. This will at least prevent the cornea from drying out due to poor eyelid closure. However, ophthalmoplegia progressiva externa cannot be cured. Among the sequelae requiring treatment, serious disorders of the endocrine glands and conduction to the heart may occur. Both of them entail further diseases. Diabetes, polyneuropathy, or dementia may develop as a result of ophthalmoplegia progressiva externa.
Treatment and therapy
To date, no causative therapy exists for the treatment of the genetic disorder ophthalmoplegia progressiva externa and its special form ophthalmoplegia plus. For this reason, the disease is considered incurable and is treated only symptomatically and supportively. Symptomatic treatment usually corresponds to the administration of high doses of coenzymes Q10, also known as ubiquinone. Substitution with carnitine or creatine is also among the general treatment recommendations for mitochondriopathies. This can improve muscular symptoms, especially in the plus form of the disease. Further treatment depends on the predominant symptomatology. Symptoms such as sensorineural hearing loss can be addressed, for example, by implanted hearing aids. If persistent cardiac arrhythmias are present in addition to the ocular symptoms, the use of a pacemaker is indicated.For final resolution of progressive cardiomyopathy, heart transplantation may be considered. To improve ataxic manifestations and muscle weaknesses of the extremities, the patient can follow physiotherapeutic measures and strengthen the affected muscles if necessary. If diabetes is also present, an appropriate diet is recommended. Patients in this case must also be provided with insulin. Care for the parents by a psychotherapist may be considered as a supportive measure. The patient himself may also benefit from psychotherapy or exchange with other affected persons, as can take place in a supportive help group.
Outlook and prognosis
The condition called ophthalmoplegia progressiva externa is a paralysis of at least one eyelid that affects the eye. Chronic progressive external ophthalmoplegia (CPEO) is usually inherited. Over the years, the paralysis of the external eye muscles and the eyelid elevator muscle increases. The visible consequences of ophthalmoplegia progressiva externa can be alleviated surgically. However, ophthalmoplegia progressiva externa is not curable. Current studies are trying to improve mitochondrial dynamics in selected subjects. Surgical procedures have been tried and tested because the affected eye cannot be completely closed due to the paralysis. Therefore, a so-called exposure keratopathy could develop in the long run due to desiccation of the cornea. Additional symptoms only occur if the so-called Ophtalmophlegia Plus is present. This variant of ophtalmophlegia is characterized by additional physical symptoms besides the typical drooping eyelid. For example, the muscles of the face, the extremities or the swallowing apparatus may be weakened. If cardiac arrhythmia is present, a pacemaker can be used nowadays. 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 sustained low-symptom state is that the therapeutic approaches pursued are also effective.
Prevention
The reasons for the disease-causing gene mutation have not yet been conclusively determined. For this reason, ophthalmoplegia progressiva externa cannot yet be actively prevented.
Follow-up
Because ophthalmoplegia progressiva externa is a genetic disease, it usually cannot be completely cured. For this reason, only a few and usually very limited aftercare measures are available to the affected person. The affected person should first and foremost consult a doctor at an early stage in order to prevent the occurrence of further complications and complaints. As a rule, self-healing is not possible. If the affected person or parents wish to have children, genetic testing and counseling should always be performed to prevent recurrence of ophthalmoplegia progressiva externa. Sufferers of the disease are dependent on regular checks of the internal organs, and the heart in particular should be checked. 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 affected person should always pay attention to a correct dosage and also to a regular intake. Many patients are also dependent on psychological support from their own family. Possibly, the disease leads to a reduced life expectancy of the affected person.
What you can do yourself
Because ophthalmoplegia progressiva externa is a genetic disease, the options for self-help are few. However, although there is no causative therapy, measures accompanying medical treatment can and should be implemented. Doctors and physiotherapists provide instructions for exercises that can be performed independently at home. This provides the opportunity to strengthen the muscles weakened by the disease and to improve the patient’s body image. 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 cope with the effects of the disease. In this context, care by a psychotherapist can benefit patients as well as parents and relatives. Through the therapists, self-help measures can be learned to reduce the stress experienced as a result of ophthalmoplegia progressiva externa. Since such a disease is an extreme situation for a family, emphasis should be placed on compensatory activities. Physical activity, if possible in the fresh air, can prevent depression and provide a better quality of life. The social environment of the ill person and his family should not be neglected either. An intact social network can help to cope with the effects of the illness and to gain new courage to face life.
