Progressive external ophthalmoplegia is also known as ophthalmoplegia progressiva externa and is one of the neuroophthalmologic disorders. A special form of the disorder is ophthalmoplegia plus (CPEO plus).
What is progressive external ophthalmoplegia?
Progressive external ophthalmoplegia is caused by a disorder of the mitochondria. This mitochondriopathy causes a slowly progressive paralysis of the external eye muscles. The eyelid elevator is also affected by the paralysis. If further symptoms occur, CPEO plus is present. There is no cure for the disease. Although the disease is inherited, it can break out at any age. The following applies: The earlier the first symptoms appear, the more severe the course of the disease. Treatment is therefore purely symptomatic.
Causes
The cause of progressive external ophthalmoplegia is mitochondriopathy. Mitochondriopathies are diseases caused by damage to or malfunction of mitochondria. Mitochondria are cell organelles that provide energy in the form of ATP. Without ATP, cells are no longer supplied with sufficient energy. Inherited mitochondriopathies result from gene mutations. The enzymes and metabolic pathways of the cell organelle are affected. Various mutations and losses of DNA segments (deletions) at position 3243 of the mtDNA have been identified as the cause of progressive external ophthalmoplegia. These defects of the mitochondrial DNA cause disturbances in the mitochondrial respiratory chain. In CPEOplus, two to eight kb deletions are found in half of the cases. Very rarely, duplications of mitochondrial DNA are also observed. In rare cases, autosomal recessive cases with nuclear gene alterations occur. In these cases, multiple deletions of mtDNA occur.
Symptoms, complaints, and signs
A characteristic sign of the disease is a drooping eyelid. In medical terminology, this phenomenon is also known as ptosis. Ptosis results from paralysis of the levator palpebrae superioris muscle. Usually, both eyes are affected by this paralysis. The mobility of the eyes is severely limited due to the paralysis of the external eye muscles. Unlike diseases associated with central gaze paralysis, in progressive external ophthalmoplegia all eye-moving brainstem functions such as optokinetics, vestibulo-ocular reflex and saccades are intact. However, because of the severe paralysis of the eye muscles, they cannot be performed as quickly. In CPEOplus, the symptoms are complemented by other muscular weaknesses. These are particularly evident in the extremities, face and swallowing muscles. Affected patients suffer from difficulty swallowing and muscle weakness in the arms and legs. The conduction of the heart is disturbed, resulting in cardiac arrhythmias. Cardiomyopathies with angina pectoris, fainting or embolisms can also be symptoms of CPEOplus. Endocrinopathies also develop, which can manifest themselves in the form of diabetes mellitus, delayed puberty or as short stature. Affected patients also suffer from sensory disturbances, peripheral paralysis or changes in the skin. Dementia or disturbances in movement coordination are also possible consequences of CPEOplus. The transition to Kearns-Sayre syndrome, a CPEO with degenerative changes of the retina, is fluid. If the central nervous system is affected by the disease, there may be sensorineural hearing loss, mental retardation, or so-called cerebellar ataxia.
Diagnosis and course of the disease
The leading finding in progressive external ophthalmoplegia is lactic acid overload. This condition is also known as lactic acidosis. In a metabolic diagnostic, urinary organic acids and blood serum amino acids are determined in addition to lactic acid levels. Creatine kinase, lactate dehydrogenase, resting lactate and pyruvate should also be measured in the blood. Neurologic examinations, electromyography, and a muscle biopsy confirm the diagnosis. Determination of thyroid hormone and antibody status is strongly recommended, as is electroneurography. Often, however, the clinical signs of progressive external ophthalmoplegia are so clear that a relatively certain diagnosis can already be made on the basis of the symptoms.However, differential diagnosis must exclude myasthenia, gaze paralysis, brainstem lesions, senile ptosis, fibrosis syndrome, and oculomotor nerve paresis.
Complications
Because of the disease, affected individuals suffer from various paralyses and disturbances of sensibility. In particular, the eyelids are affected by the paralysis, so that they can no longer be moved easily. Likewise, the paralysis can also affect the eyes themselves, so that the affected person can no longer move his eyes in different directions. The patient’s quality of life is considerably restricted and reduced by the disease. Likewise, muscle weakness and also heart problems occur. The affected person continues to suffer from swallowing disorders, so that there is significant discomfort when taking liquids and food. Diabetes or short stature can also occur. The development of children is severely delayed and disturbed by the disease, so that severe complications or discomfort usually occur in adulthood as well. Furthermore, puberty of affected individuals is often delayed as well. Since in many cases the patients also suffer from increased retardation, they are often dependent on the help of other people in their daily lives. Possibly, this disease also results in a significantly reduced life expectancy of the patient.
When should you see a doctor?
The first and most characteristic sign of progressive external ophthalmoplegia is a drooping eyelid in sufferers. A visit to the doctor should be initiated immediately if this visual feature develops. Restrictions in vision, disturbances in eye movements, and a paralytic appearance are worrisome. They should be examined and treated by a physician as soon as possible. A doctor should be consulted if there is an increase in falls, an increase in the risk of accidents, and impaired vision. If the affected person suffers from a weakness of the muscle strength, a low physical performance or a decrease of the usual resilience, a doctor should be consulted. Complaints of the swallowing act, a refusal to eat or an undersupply of the organism must be clarified by a doctor. Dysfunction, growth retardation or delayed onset of puberty should be discussed with a physician. In case of abnormalities of the natural movements, a reduced mental competence and disturbances of the memory activity a doctor is needed. Sensitivity disorders, changes in the usual skin appearance and ataxia should be examined by a doctor as well as treated. In particular, abnormalities in the coordination of movements should be understood as a warning signal of the organism. Disturbances of the heart rhythm and consciousness must also be examined. In severe cases, an ambulance service should be alerted.
Treatment and therapy
Progressive external ophthalmoplegia cannot be cured. Drooping eyelid is usually treated surgically. In most cases, surgical frontal suspension with silicone is performed. Surgical treatment of ptosis is not only done for aesthetic reasons. If the eyelid is not closed or is incomplete, the cornea may dry out. The result would be exposure keratopathy. If patients have double vision, prism glasses can help. In severe cases, however, strabismus surgery may be necessary. However, since in most patients both eyes are affected by the paralysis, strabismus is a symptom that is rarely encountered. In some patients with progressive external ophthalmoplegia, a primary deficiency of coenzyme Q10 has been demonstrated. In this case, therapy with 50 to 300 milligrams of coenzyme Q10 per day may be promising. This treatment is intended to bypass the defects in the respiratory chain so that sufficient production of ATP is possible despite the defects. Preparations such as riboflavin, L-carnitine, idebenone, or creatine monohydrate are also used to treat the condition.
Prevention
Progressive external ophthalmoplegia is a hereditary disease. Thus, it cannot be prevented. However, some studies show that the underlying mitochondriopathy develops and/or worsens preferentially when the organism is stressed by environmental factors.Harmful factors such as smoking or exposure to pollutants should therefore be avoided in cases of known mitochondriopathy.
Follow-up
The disease can be strengthened with a positive mood and emotional stability of the affected person. Especially in the bad cases, sufferers should always try to keep an uplifted mood. The things that were enjoyed before the disease should be planned and undertaken again with the social environment. Contact with family members should always be maintained by affected persons. In this way, help and support can always be requested from relatives if necessary. Affected persons must attend the regularly scheduled examinations so that the state of health can be determined by a doctor. The disease can also affect the diet. For this reason, it is important that those affected pay attention to a vitamin-rich and balanced diet. In order not to aggravate the disease, it is imperative that affected persons avoid substances containing alcohol and nicotine. To help sufferers learn how to deal with the disease appropriately, long-term psychological counseling is recommended. Going to a self-help group is also beneficial. In this way, sufferers can exchange ideas with others who also suffer from the disease and find other ways of dealing with it. This increases the quality of life of those affected, which has been greatly reduced by the disease.
What you can do yourself
Progressive external ophthalmoplegia can be countered in everyday life primarily by a positive attitude toward life. This is especially true for the more severe cases, which involve weaknesses other than eye muscles, such as swallowing or extremities. For the patients, regular diagnostic examinations are indispensable to determine the health status. The physician analyzes the values and determines how severely the muscles and, if applicable, the heart are affected. In some cases, the disease has a negative effect on the intake of food. It is therefore all the more important to ensure a balanced diet in order to prevent possible symptoms such as diabetes. To ensure that the quality of life does not suffer too much, psychotherapeutic treatment is recommended. Both children and adults feel restricted in their activities. Especially during puberty, which is usually delayed by the disease, self-esteem drops. That is why those affected should learn to accept help from other people. Support from relatives and friends has great practical benefits, especially in the context of the increased risk of accidents due to weakened vision.
