[Hereditary optic neuropathy associated with demyelinating diseases of the central nervous system]. / Nasledstvennaya opticheskaya neiropatiya v sochetanii s demieliniziruyushchimi zabolevaniyami tsentral'noi nervnoi sistemy.

Demyelinating optic neuritis and hereditary optic neuropathy (HON) take a leading place among the diseases, the leading clinical syndrome of which is bilateral optic neuropathy with a simultaneous or sequential significant decrease in visual acuity. Optic neuritis can occur at the onset or be one of the syndromes within multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD). HON are a group of neurodegenerative diseases, among which the most common variants are Leber's hereditary optic neuropathy (LHON), associated with mitochondrial DNA (mtDNA) mutations, and autosomal recessive optic neuropathy (ARON), caused by nuclear DNA (nDNA) mutations in DNAJC30. There are phenotypes of LHON «plus¼, one of which is the association of HON and CNS demyelination in the same patient. In such cases, the diagnosis of each of these diseases causes significant difficulties, due to the fact that in some cases there are clinical and radiological coincidences between demyelinating and hereditary mitochondrial diseases.

Leber Mitochondrial Optic Neuropathy in Pediatric Females With Focus on Very Early Onset Cases.

The aim of this study was to describe the phenotype of Leber hereditary optic neuropathy occurring in pediatric females. This disease generally affects young adult males, but it can occur also in females, and research data in this population is lacking. The very early onset can challenge the diagnosis and delay treatment. We searched PubMed through February 2021 and identified 226 pediatric females with genetically confirmed Leber hereditary optic neuropathy and added a new case of a 3-year-old female. The male-female ratio was 1.8:1; the mean onset age in females was 11 years with the onset at 3 years of age occurring in 3 females only. Acute onset with mild visual impairment was the most common presentation, associated with optic disc edema in 16%. Differential diagnoses are pseudotumor cerebri, optic nerve drusen and optic neuritis. The outcome is poor with partial recovery in 50%, despite some receiving Idebenone therapy.

A Tale of Progressive Painless Vision Loss in a 64-Year-Old Man Due to Leber Hereditary Optic Neuropathy.

ABSTRACT: A 64-year-old man presented with painless sequential bilateral vision loss, consistent with optic neuropathy, over the span of months. The significant decline in his visual function was out of proportion to the appearance of the optic nerves (which were not pale) or changes in his retinal nerve fiber layer thickness on optical coherence tomography. Neuroimaging revealed only mild T2 signal abnormality and faint enhancement in the left optic nerve. Extensive workup for potential infectious, metabolic, inflammatory, and ischemic etiologies was unremarkable. Empiric treatment with intravenous steroids did not slow or ameliorate the vision loss. Ultimately, genetic analysis revealed a missense m.11778G>A mutation in mitochondrial MT-ND4 gene, consistent with Leber hereditary optic neuropathy. Initiation of multivitamin supplements and idebenone unfortunately did not result in recovery of vision.

COINCIDENCE OF IDIOPATHIC INTRACRANIAL HYPERTENSION AND LEBER HEREDITARY OPTIC NEUROPATHY. A CASE REPORT.

GOAL: This paper describes a case of a long-term monitoring of a patient with optic nerve swelling on the ocular background (papilledema), accompanied by symptoms of intracranial hypertension, on whom a genetic examination was performed as part of differential diagnosis, confirming Leber Hereditary Optic Neuropathy with the m.3460G>A mutation. Casuistry: During the examination of a 5-year-old patient after an alleged head injury at a bouncy castle, an optic nerve papilla with unclear boundaries was described on the ocular background of both eyes. Neurological examination, including brain Magnetic Resonance Imaging, was indicated to rule out possible intracranial hypertension. Both examinations yielded a finding within the norm. After eight years of regular follow-up, the patient attended to our clinic with acute problems in terms of sudden visual impairment during baseball training. The performed eye examination revealed a deterioration of the vision of the right eye on counting fingers to 50 cm, vision of the left eye to 0.4 naturally, a slowed photoreaction of the right pupil, prominent optic nerve papilla with unclear boundaries on both eyes, dilated and more coiled vessels with a crossing phenomenon, the retinal periphery shows no focal changes. Due to the swelling of the papilla, acute deterioration of the vision and the suspected intracranial hypertension, the patient was immediately referred for neurological examination and subsequent hospitalization. There, the patient underwent computer tomography of the brain, venography of the dural venous sinuses and an initial laboratory examination that showed no pathology. There was increasing headache, nausea and vomiting throughout the period. A lumbar puncture was performed. The cerebrospinal fluid pressure before sampling was 285 mmH2O and 100 mmH2O after sampling. The biochemistry of the fluid was normal with negative microbiology. Evoked visual potentials had bilaterally prolonged latencies, which corresponds to optic nerve compression. An ophthalmological examination ruled out a drusen papilla. Using Optical Coherence Tomography, a 600 μm edema was detected. The patient underwent two relieving lumbar punctures, which led to a subjective improvement without objective improvement. Finally, the neurosurgeon referred the patient for ventriculoperitoneal drainage. Due to the impaired vision and lack of response to the therapy induced, a genetic test was performed, which confirmed Leber Hereditary Optic Neuropathy with the mutation of m.3460G>A. CONCLUSION: Despite the substantially improved identification of the Leber Hereditary Optic Neuropathy, the diagnosis may still be significantly delayed. The variability of initial findings, the rare incidence of the disease and few well-defined symptoms of the disease lead to significant diagnostic difficulties and late commencement of treatment. It is not possible to say whether there was a coincidence of IIH and LHON or whether the signs of IIH are a possible concomitant of the acute phase of LHON.

Leber hereditary optic neuropathy and dystonia overlapping mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes due to m.14459G>A mutation.

OBJECTIVE: To report a Chinese family with combined m.14459G>A mutation and m.6064A>T mutation of which the female proband presenting unique Leber hereditary optic neuropathy and dystonia (LDYT) overlapping mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) phenotype. METHODS: Clinical information of the pedigree was collected. We performed muscle biopsy and whole-length mitochondrial DNA (mtDNA) sequencing on the proband. The activity of respiratory chain complexes in immortalized lymphoblasts was determined. RESULTS: The current 23-year-old proband suffered from vision decline at age 15 and developed seizures and dystonia with bilateral lesions in precentral gyri at age 18. When she was 21, the lesions in bilateral putamen were found with elevated cerebrospinal fluid lactate. Her mother had optic atrophy; one of her brother died at age 4 with respiratory distress; and the other 8-year-old brother was asymptomatic. Muscle biopsy of the proband was unremarkable. The mtDNA sequencing revealed a heteroplasmic m.14459G>A mutation and a previously unreported m.6064A>T mutation. The respiratory chain complex I activity in the proband's immortalized lymphoblasts was 50% less than the normal control; while there was no statistical difference between the proband and the normal control in the activity of complex IV. CONCLUSIONS: We presented the first case exhibiting LDYT and MELAS phenotype with m.14459G>A mutation, and the decreased complex I activity contributed to the pathogenicity. Our study expanded the clinical spectrum of m.14459G>A mutation.

Late-onset Leber's hereditary optic neuropathy presenting with longitudinally extensive myelitis harbouring the m.14484T>C mutation: Extending the genotype-phenotype spectrum.

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease leading to visual loss, typically in young men, and rarely displays extra-ocular manifestations including spinal cord disease. We report the case of a 57-year-old man who presented with a longitudinally extensive dorsal column lesion as the first manifestation of LHON, with the onset of bilateral progressive optic neuropathy 11 months later, harbouring the m.14484T>C mutation. To our knowledge this is the most extensive cord lesion preceding optic neuropathy traversing the cervical and thoracic cord. We review the literature of all published cases of LHON in which spinal cord involvement was the presenting feature of the disease, summarising the clinical phenotype, demographics, radiological characteristics and genotype. We highlight the importance for diagnostic vigilance in patients with either longitudinally extensive dorsal column myelopathy, optic neuropathy or both.

What are the characteristics and progression of visual field defects in patients with Leber hereditary optic neuropathy: a prospective single-centre study in China.

OBJECTIVE: To study the characteristics and progression of visual field defects in patients with Leber hereditary optic neuropathy. DESIGN: Prospective study. SETTING: 3-A-class hospital in China; single-centre study. PARTICIPANTS: From 100 patients diagnosed with Leber hereditary optic neuropathy, 80 (160 eyes; 68 men and 12 women; youngest patient, 6 years; oldest patient, 35 years) were recruited. EXPOSURE: All patients were followed up for at least 12 months. Each patient underwent at least three visual field examinations. Patient groups 1-6 were created according to the time of visual field data acquisition. Patient group 7 included patients with a different onset of disease between eyes. Group 8 was composed of patients with a course of disease of 12-24 months when one of the examinations performed. Patients who performed the third examination made up patient group 9. PRIMARY OUTCOME MEASURES: Prevalence of the different visual field defect types on the basis of severity in groups 1-6. Mean of the difference of visual function between eyes in group 7. RESULT: In groups 1-6, the prevalences of defects classified using Visual Field Index values were significantly different between groups 1 and 3. In group 7, with the prolongation of the course of the disease, the mean of the difference of visual function between eyes decreased. There was no significant correlation between age and the severity of visual field defect. There was significant correlation between visual acuity and the severity of visual field defect. CONCLUSION: Visual field defects in patients with Leber hereditary optic neuropathy (G11778A) may continuously progress within 6 months of disease development, and remain stable after 9 months. With the progression of the disease, the differences in visual function between eyes may decrease. The severity of visual field defect seems to be independent of age; however, could be related to visual acuity. TRIAL REGISTRATION NUMBER: NCT03428178, NCT01267422.