[Chronic Progressive External Ophthalmoplegia Ptosis: Problems with Diagnostics and Treatment]. / Ptosis bei chronisch progressiver externer Ophthalmoplegie: diagnostische Probleme und therapeutische Konsequenzen.

Ptosis is often the first symptom of chronic progressive external ophthalmoplegia (CPEO), a rare muscle disorder. As the disease progresses, it can lead to ocular motility defects. Ptosis is present in the early stages of the disease and can be corrected by levator surgery. Due to the rarity of CPEO (< 1% of ptosis patients), further diagnostic steps with muscle biopsy and genetic analysis of mitochondrial DNA are usually not considered in the early phase. Intraoperative abnormal observations during ptosis surgery and postoperative motility problems are signs of CPEO. If CPEO is confirmed, alternative surgical methods can correct the ptosis, like frontalis suspension.

[Diagnosis and therapy of mitochondrial diseases]. / Mitochondrialis betegségek diagnosztikája es terápiája.

Mitochondrial diseases are a significant part of neuromuscular diseases. Majority of them is multisystemic disorder. The diagnosis can be established in more and more cases. Beyond the routine neurological examination imaging methods (MRI and MR-spectroscopy) and electrophysiology (EMG, ENG, EEG, evoked potential tests) might be helpful in setting the diagnosis. Raised blood lactate level supports the diagnosis. Muscle biopsy demonstrates mitochondrial abnormalities in the majority of cases. The positivity of genetic tests is low, because the amount of mitochondrial DNA alterations is different in tissues. Therefore other tissue than blood (mainly muscle) is necessary for genetic tests. The other reason is that the respiratory chain is under double -mitochondrial and nuclear - genetic control, and testing the nuclear genes are available only in selected laboratories. The treatment is limited, mainly symptomatic.

[Chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome : interdisciplinary diagnosis and therapy]. / Chronisch-progressive externe Ophthalmoplegie und Kearns-Sayre-Syndrom : Interdisziplinäre Diagnostik und Therapie.

BACKGROUND: The main symptom of chronic progressive external ophthalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS) are upper eyelid ptosis and a slowly progressive weakness of the extraocular muscles. Mitochondrial disorders are much more frequent than previously assumed. Because of great phenotypic variability, early diagnosis may prove to be difficult. MATERIAL AND METHODS: Retrospective analysis of 30 patients with CPEO or KSS with regard to ophthalmological and neurological findings as well as molecular genetic background. RESULTS: Twenty-seven patients presented with upper eyelid ptosis as the first clinical symptom. In 11 of these patients, ptosis was either unilateral or asymmetric. External ophthalmoplegia was present in only three patients initially; however, it developed in 27 patients in the later course of the disease. Diplopia was found to be more frequent than previously assumed. Twenty-six patients showed characteristic histological hallmarks in skeletal muscle biopsy. In 22 patients, molecular genetic testing revealed mitochondrial DNA mutations. CONCLUSIONS: Mitochondrial disorders should be included in the early differential diagnosis of patients with etiologically unclear acquired isolated unilateral or bilateral ptosis, atypical eye movement disorders, or diplopia. A correct diagnosis is mandatory for qualified counseling and the management of potentially life-threatening complications, such as cardiac involvement.

Mitochondrial disorders of the retinal ganglion cells and the optic nerve.

OBJECTIVES: To summarise and discuss recent findings and future perspectives concerning mitochondrial disorders (MIDs) affecting the retinal ganglion cells and the optic nerve (mitochondrial optic neuropathy. MON). METHOD: Literature review. RESULTS: MON in MIDs is more frequent than usually anticipated. MON may occur in specific as well as non-specific MIDs. In specific and non-specific MIDs, MON may be a prominent or non-prominent phenotypic feature and due to mutations in genes located either in the mitochondrial DNA (mtDNA) or the nuclear DNA (nDNA). Clinically, MON manifests with painless, bilateral or unilateral, slowly or rapidly progressive visual impairment and visual field defects. In some cases, visual impairment may spontaneously recover. The most frequent MIDs with MON include LHON due to mutations in mtDNA-located genes and autosomal dominant optic atrophy (ADOA) or autosomal recessive optic atrophy (AROA) due to mutations in nuclear genes. Instrumental investigations for diagnosing MON include fundoscopy, measurement of visual acuity, visual fields, and color vision, visually-evoked potentials, optical coherence tomography, fluorescein angiography, electroretinography, and MRI of the orbita and cerebrum. In non-prominent MON, work-up of the muscle biopsy with transmission electron microscopy may indicate mitochondrial destruction. Treatment is mostly supportive but idebenone has been approved for LHON and experimental approaches are promising. CONCLUSIONS: MON needs to be appreciated, requires extensive diagnostic work-up, and supportive treatment should be applied although loss of vision, as the most severe outcome, can often not be prevented.

Chronic progressive external ophthalmoplegia: a report of 6 cases and a review of the literature.

INTRODUCTION: Chronic progressive external ophthalmoplegia is a common mitochondrial disease that shares clinical, enzymatic, and genetic features with other mitochondrial disorders. Effective treatment does not exist, and corrective surgery of the ptosis as a palliative measure is a treatment option. PATIENTS AND METHODS: This was a retrospective study of 10 years' duration gathering patients with the diagnosis. Information related to clinical features, ancillary tests, and genetic data was obtained from our patients. RESULTS: Six patients were identified with this disease, 5 of them women, aged 44 to 72 years. All patients presented with ptosis, and in 50% of the patients it was asymmetric. Half of the patients noted mild dysphagia for liquids. The CPK and acetylcholine receptor antibody levels were normal. Jitter was increased in half of the patients and ragged-red fibers were present in 5 of them. The most common enzyme alteration was the combined deficit of complexes I and IV. Familial forms were not found among our patients. The most common genetic anomaly was a single deletion in the mitochondrial DNA. CONCLUSION: Knowledge of this disorder enables us to avoid the use of drugs with significant side effects in cases of ptosis and ophthalmoplegia that do not respond to anticholinesterases.

Update on chronic progressive external ophthalmoplegia.

Mitochondrial encephalomyopathies are clinically and genetically heterogeneous disorders. External ophthalmoplegia is the most frequent symptom. Other frequently involved tissues and organs include the retina, heart, limb muscles, peripheral and central nervous system, inner ear and endocrine system. The diagnosis is based on the finding of elevated serum lactate, the characteristic histopathological changes in the muscle biopsy, and decreased activities of mitochondrial respiratory chain enzymes. In many cases, the underlying molecular defect in the mtDNA can be identified. The efficacy of pharmacological therapies (e.g., coenzyme Q) has not been established so far. Symptomatic ophthalmological treatment includes ptosis and strabismus surgery. Early cardiac pacemaker implantation may be life-saving.

Bilateral spontaneous corneal perforation associated with complete external ophthalmoplegia in mitochondrial myopathy (kearns-sayre syndrome).

PURPOSE: Mutations of mitochondrial DNA can lead to a variety of pheno- and genotypically heterogeneous diseases. Kearns-Sayre syndrome is caused by the deletion of several mitochondrial genes. The syndrome is characterized by chronic progressive external ophthalmoplegia, tapetoretinal degeneration, and severe generalized myopathy. CASE REPORT: We report on a 36-year-old female patient with Kearns-Sayre syndrome, confirmed by biochemistry, histology, and genetics. Over a period of 10 years, progressive ophthalmoplegia led to recurrent conjunctivitis, keratitis, and corneal ulceration. Almost total external ophthalmoplegia including involvement of the orbicularis oculi muscles was observed. Despite advanced ptosis, there was lagophthalmos of 2 mm with near complete extinction of globe motility in both eyes. The left eye showed a peripheral corneal perforation parallel to the lower limbus. After successful penetrating keratoplasty in the left eye, despite preventive measures, a peripheral corneal perforation also occurred in the right eye. Penetrating keratoplasty was therefore also performed on the right eye. To achieve a satisfactory functional result, large-diameter transplants were necessary in both eyes. To prevent immune reactions, cyclosporine therapy was initiated prophylactically. Sixteen and 9 months after penetrating keratoplasty, the corrected visual acuity was 20/60 in the right eye and 20/100 in the left eye, with clear transplants on both sides. DISCUSSION: Patients with progressive ophthalmoplegia require thorough neurologic investigation and evaluation. Lagophthalmos in the presence of almost absent globe motility requires extensive preventive measures to avoid exposure keratitis. In spite of this, in the presented case, corneal perforation of the second eye could not be prevented.

Congenital mitochondrial cytopathy and chronic progressive external ophthalmoplegia.

BACKGROUND: Chronic Progressive External Ophthalmoplegia (CPEO) encompasses different conditions having in common a slowly progressive external and general ophthalmoplegia. The discovery of CPEO is suggestive of mitochondrial cytopathy, but this is not necessarily so. CASE REPORT: We report here a case, presenting at age 9 months, characterized by bilateral blepharoptosis and partial third nerve oculomotor deficiency, with no nystagmus. Mitochondrial cytopathy was suspected on cranial MRI and confirmed by muscle biopsy. Enzyme studies revealed a defect on the complex I respiratory chain. This case is unique in that the symptoms completely resolved under a Ketogen diet.

[Observation on therapeutic effect of acupuncture combined with western medicine on paralytic strabismus].

OBJECTIVE: To find out a better therapy for paralytic strabismus. METHODS: Ninety cases were randomly divided into an acupuncture-medicine group, an acupuncture group, a western medicine group, 30 cases in each group. The acupuncture-medicine group were treated with acupuncture at Shuigou (GV 26), Fengchi (GB 20), Yifeng (TE 17), Yiming (EX-HN 14), Taiyang (EX-HN 5), Jingming (BL 1), Cuanzhu (BL 2), etc. intramuscular injection of Vit B1 and Vit B12, and oral administration of ATP; the acupuncture group were treated with simple acupuncture, and the western medicine group were treated with simple western medicine. Their therapeutic effects were compared. RESULTS: The cured rate of 66.7% in the acupuncture-medicine group was significantly higher than 26.7% in the acupuncture group and 26.7% in the western medicine group (both P < 0.01). CONCLUSION: Acupuncture combined with western medicine has obvious therapeutic effect, which is better than that of simple acupuncture or simple western medicine.

[Gene expression profiling of classic mitochondrial disorders. Its value in finding therapeutic strategies]. / Genexpressionsstudien bei klassischen Mitochondriopathien. Eine Hilfe bei der Suche nach therapeutischen Strategien?

Mitochondria are semiautonomous cell organelles which possess their own genome (mtDNA) but nonetheless depend on the import of nuclear-encoded proteins. In recent years, several mutations of mtDNA have been associated with specific diseases of the muscles and nervous system. In 1993, the A>G point mutation at position 3243 of the mtDNA, until then a prominent genetic marker for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), was detected in patients with progressive external ophthalmoplegia (PEO). Due to the divergent clinical presentations of MELAS and PEO, the presence of potential nuclear secondary mutations or so-called modifier genes had been suspected. Now it is well known that a bidirectional information flow between the mitochondrion and the cell nucleus exists and that nuclear gene expression adapts to the functional status of the mitochondria. However it remains unclear when and how the nucleus responds to changes or mutations of the mtDNA and if there are indeed disease-specific biomarker genes whose expression changes in case of mtDNA aberrations. This review article focuses on the most recent gene expression profiling studies in the field of classic mitochondrial disorders.

Adeno-associated virus-mediated gene transfer of the heart/muscle adenine nucleotide translocator (ANT) in mouse.

Mitochondrial myopathy, associated with muscle weakness and progressive external ophthalmoplegia, is caused by mutations in mitochondria oxidative phosphorylation genes including the heart-muscle isoform of the mitochondrial adenine nucleotide translocator (ANT1). To develop therapies for mitochondrial disease, we have prepared a recombinant adeno-associated viral vector (rAAV) carrying the mouse Ant1 cDNA. This vector has been used to transduce muscle cells and muscle from Ant1 mutant mice, which manifest mitochondrial myopathy. AAV-ANT1 transduction resulted in long-term, stable expression of the Ant1 transgene in muscle precursor cells as well as differentiated muscle fibers. The transgene ANT1 protein was targeted to the mitochondrion, was inserted into the mitochondrial inner membrane, formed a functional ADP/ATP carrier, increased the mitochondrial export of ATP and reversed the histopathological changes associated with the mitochondrial myopathy. Thus, AAV transduction has the potential of providing symptomatic relief for the ophthalmoplegia and ptosis resulting from paralysis of the extraocular eye muscles cause by mutations in the Ant1 gene.

Combination ptosis crutch and moisture chamber for management of progressive external ophthalmoplegia.

BACKGROUND: A 46-year-old woman with a long-standing history of chronic progressive external ophthalmoplegia manifested a primary visual symptom of bilateral ptosis. Previous lid surgery was unsuccessful because of severe sight-threatening exposure keratitis. CASE REPORT: The patient's problem was managed by fabricating a spectacle-mounted combination ptosis crutch and moisture chamber. The custom device successfully provided both cosmetic and visual relief for the patient while maintaining corneal integrity. CONCLUSIONS: This case demonstrates the effectiveness of a dual-purpose appliance that offers a cosmetically viable alternative to ptosis patients who are high-risk surgical candidates because of potential corneal dehydration.

Chronic progressive external ophthalmoplegia.

Chronic progressive external ophthalmoplegia (CPEO) is a descriptive term for a heterogenous group of disorders characterized by chronic, progressive, bilateral, and usually symmetric ocular motility deficit and ptosis. Significant pain, proptosis, or pupil involvement are not features of CPEO and should prompt evaluation for alternative etiologies. Mitochondrial DNA mutations are increasingly being recognized as the etiology for CPEO syndromes. Clinicians should recognize the specific syndromes associated with CPEO, characterized by variable systemic, neurologic, or other findings. Treatment is limited, but newer therapies are being investigated.

Oftalmopatía distiroidea / Dysthiroid Ophtalmopathy

La oftalmopatía distiroidea es la causa más frecuente de proptosis uni o bilateral en el adulto. Afecta con más frecuencia a las mujeres entre los 25 y los 50 años, aunque el curso es más agresivo en los hombres. Se relaciona con hipertiroidismo (91%), tiroiditis de Hashimoto (3%) y eutiroidismo (6%). Hisotpatológicamente se observa un aumento de glucosaminoglicanos en el tejido conectivo de grasa orbitaria y músculos extraoculares. Las manifestaciones clínicas son, en orden de frecuencia, la retracción palpebral, la proptosis, la diplopia y la neuropatía óptica por compresión.