Progressive external bilateral ophthalmoplegia

In general, bilateral ophthalmoplegia chronic can be observed in processes on the supranuclear, nuclear (at the level of the brainstem), root, axonal (neural) and muscular levels. However, in practice, bilateral ophthalmoplegia often indicates a muscular lesion level or (less often) stem localization of the lesion. Intermediate level (neural), as a rule, is one-sided. Moreover, muscular lesion is characterized by a chronically progressing course (myopathy). Bilateral lesions of the oculomotor nerves at the nuclear level in the region of the brainstem are more often (but not exclusively) observed in acute processes leading to a coma.

There are detailed classifications of the syndrome of bilateral progressive external ophthalmoplegia (PNO), built mainly on the genetic principle and for the practical doctor is not very convenient. It is important to emphasize that most forms of isolated bilateral bilateral progressive ophthalmoplegia are caused by ocular myopathy of different genetic origin, that is processes on the peripheral muscular level. Bilateral ophthalmoplegia due to lesions at the neural level or neuronal (defeat of the oculomotor nerves on both sides or their nuclei in the brainstem) is extremely rare and is observed in the picture of hereditary degenerative (less often metabolic) disorders on the background of another massive neurological symptomatology.

Main reasons:

1. Mitochondrial encephalomyopathy of Kearns-Seira ("ophthalmoplegia plus").
2. Oculopharyngeal muscular dystrophy with autosomal dominant or autosomal recessive inheritance.
3. Congenital myopathies: central rod disease, non-melanoma, myotubular and others.
4. Congenital myasthenia gravis (myasthenia gravis).
5. PNO with hypogonadism.
6. PNO with neurological diseases:
   • abetalipoproteinemia,
   • spinocerebellar ataxia,
   • amyotrophic lateral sclerosis (rarely),
   • sensorimotor neuropathy with paraproteinemia,
   • progressive supranuclear palsy, other neurological diseases.

The most clinically important are the forms that begin in young and adulthood. Among them, most often there are mitochondrial forms and, especially, the Kearns-Seir disease. The mitochondrial defect in this disease is not limited only to muscle tissue, but extends to the central nervous system and internal organs.

The implications of the syndrome of Kearns-Seyr include:

1. external ophthalmoplegia;
2. pigmentary degeneration of the retina;
3. conduction disorders of the heart;
4. increase in protein content in liquor.

The first symptoms usually appear in childhood or adolescence (rarely - in adults) in the form of slowly growing ptosis; Behind him there are symptoms of ophthalmoparesis with preserved pupils. Ophthalmoparez slowly progresses to ophthalmoplegia. Uniform involvement of all external muscles of the eye leads to the fact that strabismus and doubling are observed rarely. When trying to look up the head throws back and the frontal muscles contract (face of Gatchinson). In addition to the oculomotor muscles, the circular muscle of the eye is often involved, which creates difficulties both in opening the eyes and when closing, which may resemble a picture of myasthenia gravis or myotonic dystrophy. Other facial muscles, as well as chewing, nodding, deltoid or peroneal, are involved in approximately 25% of cases. It is possible to join cerebellar ataxia, spastic paraparesis, dementia, deafness and other symptoms ("ophthalmoplegia plus").

The absence of myotonia, cataracts and endocrine disorders distinguishes progressive external ophthalmoplegia from myotonic dystrophy (which may resemble ptosis). The more extensive forms of the Kearns-Seir syndrome may resemble the fasio-skapulo-humeral form of muscular dystrophy. A characteristic feature of the syndrome of Kearns-Seyr is that ptosis and oculomotor disorders precede the involvement of other muscles.

Optional symptoms: defeat of visceral organs (heart, liver, kidneys, endocrine glands - "oculocranio-somatic syndrome").

Oculopharyngeal muscular dystrophy with autosomal dominant inheritance, associated with chromosome 14, is characterized by a late onset (usually after 45 years) and manifests itself mainly as a slow progressive bilateral ptosis and dysphagia. Thus, in addition to ptosis (ophthalmoplegia does not develop), dysphagia develops and the voice changes. Rough dysphagia sometimes leads to severe cachexia. In some families, at a later stage, the weakness of the muscles of the shoulder and pelvic girdles is added. Described "oculopharyngeal myopathy." The nuclei of the cranial nerves and the nerves themselves are not histologically altered. The level of CK is normal; EMG is changed only in the affected muscles.

Finally, families are described in which progressive external ophthalmoplegia was transmitted from generation to generation along with symptoms of hypogonadism. Some other hereditary variants of progressive external ophthalmoplegia are also possible.

Progressive bilateral external ophthalmoplegia in neurological diseases is described in several situations. Abetaliproteinemia (Bassen-Kornzweig disease) is an autosomal recessive disease characterized by an almost complete absence of beta-lipoprotein (hence, a violation of fat and vitamin E absorption) and is already manifested in infants in the first year of life by steatorrhea (fatty stool), growth retardation, retinal degeneration (decreased vision and blindness), acanthocytosis and neurologic symptoms, indicative of a predominant lesion of the cerebellum and peripheral nerves. There may be a slow progressive ophthalmoparesis.

Ophthalmoplegia as a rare symptom is also described in other neurological diseases, including hereditary spastic paraplegia, spinocerebellar degenerations (eg, Machado-Joseph disease), sensorimotor polyneuropathy (with paraproteinemia). Ophthalmoplegia is rarely seen with progressive spinal amyotrophy and even more rarely with amyotrophic lateral sclerosis.

Chronic bilateral ophthalmoplegia can be observed with glioma of the brainstem, chronic meningitis. Among the forms mentioned rare ophthalmoplegia with mitochondrial encephalomyopathies neyrogastrointestinalnoy (MNGIE - mitochondrial neurogastrointestinal encephalomyopathy) and mitochondrial encephalomyopathies with ophthalmoplegia, and pseudo polyneuropathy (MEROR-mitochondrial encephalomyopathy with ophthalmoplegia, pseudoobstruction and polineuropathy), subacute necrotizing encephalomyelopathy (Leigh disease), deficiency of vitamin E.

Among other causes of PNO, progressive supranuclear palsy should be mentioned, which may eventually lead to complete ophthalmoplegia, but the latter appears against extrapyramidal, pyramidal and sometimes mental (dementia) disorders.

Supranuclear ophthalmoplegia is also characteristic of Whiple disease (weight loss, fever, anemia, steatorrhea, abdominal pain, arthralgia, lymphadenopathy, hyperpigmentation, in the neurological status, a slowly progressing memory decline or dementia, hypersomnia, supranuclear ophthalmoplegia, ataxia, epileptic seizures, myoclonus , oculomastor myorrhythmia).

Progressive external ophthalmoplegia can sometimes be observed with myasthenia gravis (congenital and juvenile), ophthalmopathy with thyrotoxicosis (thyrotoxic ophthalmopathy), with chronic inflammation in the orbit, congenital myopathies.

If ophthalmoplegia do not respond to light, then this syndrome should be called not external, but complete (total) ophthalmoplegia. It is often acute, but we do not discuss here in detail the acute total bilateral ophthalmoplegia. Its main causes: apoplexy of the pituitary gland, botulism, midbrain hematoma, preterital infarction, Wernicke's encephalopathy, Guillain-Barre syndrome, cavernous sinus syndrome in the tumor or inflammatory process of this localization, myasthenia gravis.

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