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Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by visual loss, and rarely associated with extraocular manifestations including multiple sclerosis-like lesions. The association of LHON and neuromyelitis optica spectrum disorders has rarely been reported. Here is reported a case of glial fibrillary acidic protein astrocytopathy presenting with area postrema syndrome in a patient with previously diagnosed recessive LHON due to mutations in the nuclear gene DNAJC30. This case emphasizes the necessity of extensive investigations for other treatable conditions in patients with LHON and otherwise unexplained extraocular involvement and the possibility that also visual symptoms can respond to immune therapy., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Leber hereditary optic neuropathy (LHON) is one of the more common mitochondrial diseases and is rarely associated with mitochondrial renal disease. We report 3 unrelated patients with a background of adult-onset renal failure who presented to us with LHON and were shown to have a heteroplasmic mitochondrial DNA mutation (m.13513G>A)., Methods: Retrospective chart review., Results: All 3 patients had a background of chronic renal failure and presented to us with bilateral optic neuropathy (sequential in 2) and were found to have heteroplasmic m.13513G>A mutations in the MT-ND5 gene. Two of the patients were females (aged 30 and 45 years) with chronic kidney disease from their 20s, attributed to pre-eclampsia, one of whom also had diabetes and sudden bilateral hearing loss. One patient was a male (aged 54 years) with chronic kidney disease from his 20s attributed to IgA nephropathy. His mother had diabetes and apparently sudden bilateral blindness in her 70s. Renal biopsy findings were variable and included interstitial fibrosis, acute tubular necrosis, focal segmental glomerulosclerosis, and IgA/C3 tubular casts on immunofluorescence. Mild improvements in vision followed treatment with either idebenone or a combination supplement including coenzyme Q10, alpha-lipoic acid, and B vitamins., Conclusions: Our cases expand the clinical syndromes associated with m.13513G>A to include bilateral optic neuropathy and adult-onset renal disease. This highlights that in patients with bilateral, especially sequential, optic neuropathy a broad approach to mitochondrial testing is more useful than a limited LHON panel. Mitochondrial diseases present a diagnostic challenge because of their clinical and genetic variability., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Competing Interests: The authors report no conflicts of interest.

Competing Interests: The authors report no conflicts of interest.

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.

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 «plus», 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.

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

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.

Competing Interests: The authors report no conflicts of interest.

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., (© 2021. Fondazione Società Italiana di Neurologia.)

Introduction: Charles Bonnet syndrome is characterized by simple or complex visual hallucinations (VH) due to damage along the visual pathways. We report a functional MRI study of brain correlates of VH in the context of a severe optic atrophy in a patient with Leber's Hereditary Optic Neuropathy (LHON)., Case Report: A 62-year-old man was diagnosed with LHON (11778/ND4 mtDNA mutation) after subacute visual loss in left eye (right eye was amblyopic). One month later, he experienced VH of a few seconds consisting in "moving red and blue miniature cartoons". One year later VH content changed in colored mosaic (10-15 s duration), usually stress-related, and blue and white flashes (2-5 s), triggered by unexpected auditory stimuli. Audiometry revealed mild sensorineural hearing loss. Three block design functional MRI paradigms were administrated: 1) random "clap", 2) "checkerboard" and 3) non-random "beep". After random "claps" simple flashes were evoked with bilateral activation of primary and secondary visual cortex, cuneus, precuneus and insula. Neither hallucinations nor cortex activation were registered after "checkerboard" stimulation, due to the severe visual impairment. Primary and secondary auditory cortices were "beep"-activated, without eliciting VH by non-random "beep"., Conclusions: The peculiarity of our case is that VH were triggered by random auditory stimuli, possibly due to a cross-modal plasticity between visual and auditory networks, likely influenced by the sensorineural deafness. Functional alterations of both networks in resting conditions have been demonstrated in LHON patients, even without an auditory deficit. Finally, the absence of VH triggered by expected stimuli is consistent with the "expectation suppression theory", based on increased neural activations after unexpected but not by predicted events.

Little is known about the molecular mechanism of the rare coexistence of Leber's Hereditary Optic Neuropathy (LHON) and multiple sclerosis (MS), also known as the Harding's syndrome. In this study, we provide novel evidence that the m.11778A > G variant causes a defective metabolic interplay between mitochondrial oxidative phosphorylation and glycolysis. We used dermal fibroblasts derived from a female proband exhibiting clinical symptoms compatible with LHON-MS due to the presence of the pathogenic m.11778A > G variant at near homoplasmic levels. Our mitochondrial morphometric analysis reveals abnormal cristae architecture. Live-cell respiratory studies show stunted metabolic potential and spare respiratory capacity, vital for cell survival upon a sudden energy demand. The m.11778 A > G variant also alters glycolytic activities with a diminished compensatory glycolysis, thereby preventing an efficient metabolic reprogramming during a mitochondrial ATP crisis. Our collective results provide evidence of limited bioenergetic flexibility in the presence of the m.11778 A > G variant. Our study sheds light on the potential pathophysiologic mechanism of the m.11778 A > G variant leading to energy crisis in this patient with the LHON-MS disease., (Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Leber's hereditary optic neuropathy (LHON) is an optic neuropathy of mitochondrial inheritance, characterised by incomplete penetrance and variable expressivity. Typically, young male patients present with sequential, severe, rapidly progressive loss of central vision, with characteristic funduscopic findings. However, LHON may present at any age, in both genders, and fundus examination may be normal. Evidence has emerged to support the role of environmental factors in triggering LHON, by disrupting the normal mechanisms of mitochondrial function. We present two clinical cases of LHON of late onset, and provide a literature review on atypical cases of LHON and the role of environmental triggers., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited recessive disease rarely complicated with glaucoma. We conducted a clinical and genetic retrospective case series to describe three cases of juvenile open-angle glaucoma (JOAG) and an ND4 m11778G > A mitochondrial DNA (mtDNA) mutation, which is pathognomonic for LHON., Case Presentation: Patient 1 was a 16-year-old boy diagnosed with bilateral JOAG and high myopia. His intraocular pressure (IOP) was poorly controlled with the use of full topical anti-glaucoma medications. His best-corrected visual acuity (BCVA) decreased gradually over 5 years. Fundoscopic examination revealed bilateral enlarged disc cupping of the optic nerves with sectorial excavation and reduction of the neural rim in the left eye. His visual field (VF) was characterized by bilateral progressive central scotoma. Pattern visual evoked potentials (VEPs) and pattern electroretinograms (ERGs) showed extinguished responses in both eyes. Because of the non-specific visual field findings and the optic neuropathy disclosed by the pattern VEPs and pattern ERGs, we arranged a genetic test for the patient, which revealed an m11778G > A mtDNA mutation. Patient 2, the younger brother of Patient 1, was a 15-year-old boy who had been diagnosed with bilateral JOAG in 2010. The BCVA of both eyes remained at 1.0 during the follow-up period. Fundoscopic examination revealed bilateral mildly paled optic disc with enlarged cupping and reduction of the neural rim. The pattern ERG revealed a decreased N95 amplitude bilaterally. The genetic test revealed an m11778G > A mtDNA mutation. Patient 3 was a 35-year-old man with bilateral JOAG. His BCVA decreased gradually over 10 years. Fundoscopic examination revealed paled optic disc with enlarged disc cupping and reduction of the neural rim in both eyes. The pattern ERG revealed a decreased N95 amplitude bilaterally. The genetic test revealed an m11778G > A mtDNA mutation., Conclusions: This case series describes three patients with concomitant occurrence of JOAG and LHON. These two diseases may have a cumulative effect on oxidative stress and retinal ganglion cell death with the rapid deterioration of vision, which may occur during adolescence.

A 28-year-old Caucasian man developed sudden painless vision loss in the right eye. He was diagnosed with optic neuritis. MRI showed white matter lesions consistent with multiple sclerosis (MS), but no optic nerve enhancement. Eight months later, the left eye was affected in the same manner. Examination showed right optic atrophy and apparent left optic disc swelling. Workup revealed positive Lyme IgG. Differential diagnosis included optic neuritis and Lyme optic neuropathy, and he was treated with intravenous steroids, intravenous immunoglobulin, plasmapheresis and intravenous ceftriaxone without improvement. Neuro-ophthalmology consultation led to identification of pseudo-optic disc oedema, and Leber's hereditary optic neuropathy (LHON) was suspected and confirmed by genetic testing. LHON may occur in association with MS, and should be considered in patients with MS with vision loss atypical for optic neuritis. This is especially important as new treatments for LHON (including gene therapy) are currently undergoing clinical trials., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Leber hereditary optic neuropathy (LHON) is a rare mitochondrial genetic disorder characterized by painless acute or subacute vision loss that develops during adolescence. Clinicians should know how to identify potential LHON and when to refer patients to a neuro-ophthalmologist for diagnosis and treatment. This case highlights the value of a thorough family history in ED patients.

This report describes a 66-year-old Caucasian male who acutely developed severe, bilateral impairment of visual acuity at 24 years of age. Leber's hereditary optic neuropathy (LHON) was suspected but the diagnosis was not genetically confirmed until the age of 49 years when the primary LHON mutation m.3460G>A was detected. Since onset, visual acuity had slightly improved. The family history was positive for LHON (brother, two sisters of mother, female cousin) and genetically confirmed in his brother and one aunt. Since the age of 65 years, he had experienced recurrent vertigo. His cardiological history was positive for arterial hypertension, noncompaction, myocardial thickening, intermittent right bundle-branch-block (RBBB) and Wolff-Parkinson-White (WPW) syndrome. In addition to LHON, he presented with polyneuropathy, hyperCKaemia, carotid artery occlusion, and a history of stroke. Cardiological investigations at 66 years of age revealed mildly reduced systolic function, enlarged atria, and nonsustained ventricular tachycardias. He underwent an electrophysiological investigation, but radiofrequency ablation was ruled out due to a 'bizarre' cardiac conduction system. Instead, an implantable cardioverter defibrillator was proposed but refused by the patient. Since the vertigo did not resolve it was attributed to polyneuropathy. This case demonstrates that LHON may be associated with noncompaction, myocardial thickening, reduced systolic function, enlarged atria, RBBB, WPW syndrome and nonsustained ventricular tachycardias. WPW syndrome in LHON may require invasive antiarrhythmic treatment.

Purpose: Leber's hereditary optic neuropathy is relatively rare, and no clinical pathognomonic signs exist. We present a rare case of bilateral vision loss of a patient with multiple drug abuse in the history., Observation: A 31-year-old man presented with a history of progressive, decreased vision in both eyes for 6 month. On examination, his visual acuity was hand motion in both eyes. Funduscopy demonstrated a temporal pallor of the optic disc. Goldmann visual field perimetry showed a crescent visual field in the right eye and a circular decrease to less than 50 ° in the left eye. Electroretinogram showed a scotopic b-wave amplitude reduction. Optical coherence tomographies, Heidelberg Retina tomography, visual evoked potentials, and magnetic resonance imaging with contrast as well as blood tests were normal. The patient reported to consume various kinds of drugs as well as recreational drug use and alcohol consumption since he was 16 years old. We started a hemodilution therapy, believing the patient suffered from a bilateral, toxic optic neuropathy due to his lifestyle. Laboratory results later on showed Leber's hereditary optic neuropathy., Conclusion and Importance: Leber's hereditary optic neuropathy is a rare disease without a typical, pathognomonic presentation. Even though the patient gave good reasons for a toxic optic neuropathy, one should never stop to test for other diseases.

A 30-year-old woman with progressive vision loss was found to have asymptomatic, bilateral, and symmetric basal ganglia lesions on MRI and was later diagnosed with Leber hereditary optic neuropathy (LHON). The rare occurrence of basal ganglia changes on MRI in patients with LHON is discussed.

A 15-year-old boy experienced painless vision loss in the left eye of unknown duration. Leber hereditary optic neuropathy (LHON) was suspected, despite negative testing for the 3 most common pathogenic gene mutations and idebenone 300 mg 3 times daily was prescribed. Nine months later, the patient developed right eye involvement. Complete mitochondrial genome analysis revealed 2 rare variants-m.3890G>A of the MT-ND1 gene and m.8417C>A of the MT-ATP8 gene. The former has been described in severe infantile Leigh syndrome and LHON; the latter is of unknown significance. The patient experienced progressive visual deterioration through 12 months, but improved to 20/20, right eye and 20/25, left eye, at 21 months. Visual recovery can occur in a patient with bilateral optic neuropathy secondary to the rare m.3890G>A point mutation.

Background: Leber׳s hereditary optic neuropathy usually causes rapid bilateral blindness in young adults, and thus represents a unique and severe psychologic stressor., Objective: We aimed to describe adjustment to this major life event, using a new tool to enhance recall of past affective states by using life event-related context. This is the largest (n = 116 with Leber׳s hereditary optic neuropathy), and first study reporting on the emotional aspects of this nontrauma cause of blindness., Methods: We developed a new online survey tool that allowed study subjects to report their mood over a long period of time, corresponding with dates of relevant life events., Results: The new method provided data of great richness for qualitative and quantitative analysis. Three groups were identified: a group in which majority of them had severe sadness at the point of vision loss followed by a period of recovery, a group whose sadness had not recovered, and a group for whom vision loss was not a major cause of sadness compared with other life events. We identified numerous factors that were important in psychologic recovery, and premorbid psychologic symptoms were more frequent in those who had not yet recovered., Conclusions: These data may assist behavioral health providers in identifying patients with vision loss to be at risk of mental health problems and in developing support and treatment interventions. We believe this new method has great potential for studying psychologic adjustment retrospectively., (Copyright © 2017 The Academy of Psychosomatic Medicine. All rights reserved.)

Background: Leber's hereditary optic neuropathy (LHON) co-occuring with multiple sclerosis-like disease (LHON-MS) is suggested to be a separate disease entity denoted Harding's disease. Little is known about the response to initiation and discontinuation of potent immunomodulatory treatment in LHON-MS., Case Presentation: We describe a LHON-MS patient with 27 years disease duration who developed severe disease activity peaking 14 months after discontinuation of natalizumab, with extensive new inflammatory lesions throughout the brain and in the spinal cord resembling immune inflammatory reconstitution syndrome. She had previously been clinically and radiologically stable on natalizumab treatment for 6 years, and before that only experienced subtle clinical activity during 9 years on interferon beta1a., Conclusion: This is the first report on severe exacerbation of inflammatory disease activity after discontinuation of natalizumab in LHON-MS, and suggests that late rebound activity can occur in these patients.

A 45-year-old woman presented with acute sequential optic neuropathy resulting in bilateral complete blindness. No significant visual recovery occurred. Past medical history was relevant for severe preeclampsia with resultant renal failure, diabetes mellitus, and sudden bilateral hearing loss when she was 38 years old. There was a family history of diabetes mellitus in her mother. Testing for common causes of bilateral optic neuropathy did not reveal a diagnosis for her illness. The maternal and personal history of diabetes and deafness prompted testing for mitochondrial disease. The 3 primary mitochondrial DNA mutations responsible for Leber hereditary optic neuropathy were absent, but the patient was subsequently found to have a disease causing mitochondrial DNA mutation, m.13513G>A. The case illustrates the importance of early testing for mitochondrial disease and demonstrates that Leber hereditary optic neuropathy-like presentations may be missed if testing is limited to the 3 primary mutations., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Introduction: Retrospective study analyzing clinical characteristics and treatment of children affected by Leber-Coats' disease., Method: Children with Leber-Coats' disease seen in Edouard-Herriot Hospital, Lyon, between January 2004 and September 2013 were included. The following clinical characteristics were reported: sex, age at diagnosis, presenting symptom, Shields' stage, treatment used, and visual outcomes., Results: Ten children were included in our study. Mean age at diagnosis was 5.5 years. The disease was unilateral in 9/10 cases. The presenting symptom was loss of vision in 7/10 cases, strabismus in 3/10 cases, and microphthalmos in 1 case. The diagnosis was made fortuitously during a follow-up of familial congenital cataract in 2 patients. No cases of leukocoria were seen. Shields' stages were distributed as follows: stage 1, 2A and 2B: 1 case each, stage 3A1: 7 cases, stage>3A1: no cases. Laser photocoagulation was used up to stage 2B, combined with cryotherapy in stage 3A. Stage 1 and 2A were associated with relatively good final visual acuity. Significant macular lipid exudate (stage>2A) was associated with a worse prognosis., Conclusion: These epidemiological data help us to better characterize these patients' prognosis. Early diagnosis seems to improve visual outcomes., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

A clinical case of a young man with rapid bilateral visual impairment developed 2 months after the onset of generalized convulsive seizures is presented. The replacement of valproate to levetiracetam led to the remission of seizures, but the prognosis for vision remains poor, particularly given the pessimistic results of optical coherence tomography (OCT).

Background: Leber's hereditary optic neuropathy (LHON) and a multiple sclerosis (MS)-like illness appear to coexist 50 times more frequently than would be expected by chance. This association of LHON and MS (LMS) raises an important question about whether there could be a common pathophysiological mechanism involving mitochondrial dysfunction., Objective: The primary aim was to define MRI features of LMS and LHON, and to assess the proportions of individuals displaying features typical of MS. Secondarily, we investigated the effect of gender on the risk of developing white matter lesions in the context of LHON., Methods: A blinded standardised review of conventional brain MRIs of 30 patients with MS, 31 patients with LHON and 11 patients with LMS was conducted by three independent experts in the field. MS-like MRI features were assessed., Results: All patients with LMS and 26% of patients with LHON had white matter lesions. Of these, all patients with LMS and 25% with LHON were found to have an MRI appearance typical of MS. Female patients with LHON had a significantly greater risk of having white matter lesions consistent with MS compared with male patients (relative risk 8.3)., Conclusions: A blinded review of conventional brain MRIs shows that patients with LMS have a scan appearance indistinguishable from MS. Mitochondrial dysfunction could be a common pathophysiological pathway in the formation of white matter lesions. There appears to be a strong female influence on the radiological appearance as well as clinical development of MS in patients with LHON., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Defined involvement lesions of the digestive system of clinical manifestations of mitochondrial dysfunction associated with both point mutations and polymorphism of mitochondrial DNA. The nature of the clinical signs of mtDNA polymorphisms carriers--multi organical, a progressive, clinical polymorphism, genetic heterogeneity with predominant involvement of energotropic bodies (cerebrum, cordis, hepatic). Set individual nosological forms of mitochondrial dysfunctions--syndromes Leia, Leber, Cairns, Sarah, MERRF, MELAS, NARP, MNGIE confirmed by clinical and genetic, morphological, biochemical, enzymatic, molecular genetics methods. It was found that 84-88% of these syndromes involving the violation of the digestive system with varying degrees of injury. This damage will be the first in the complex chain signs recovery which determines the direction of early rehabilitation.

Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype., Case Presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present., Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation.

We report the first case of definite neuromyelitis optica (NMO) with a pathogenic mitochondrial DNA (mtDNA) mutation for Leber's hereditary optic neuropathy (LHON) (G11778A point mutation). A 36-year-old Japanese woman had experienced recurrent neurological symptoms originating from involvements of the optic nerves and spinal cord. She finally lost her bilateral vision, and spastic paraparesis and sensory disturbances below the T6 level remained despite intensive immunotherapies. Brain and spinal magnetic resonance imaging (MRI) revealed T2-high-intensity lesions in the optic nerves and thoracic spinal cord, but no lesions in the brain. A blood examination revealed positivity for both anti-aquaproin-4 antibodies and an LHON mtDNA mutation.

Background: Leber hereditary optic neuropathy (LHON) is characterized by progressive loss of central vision leading to impaired reading ability. The aim of this study was to evaluate sensory adaptation and reading ability in LHON patients., Methods: This prospective pilot study included 12 male patients with a clinical diagnosis and a positive genetic analysis of LHON, who matched the inclusion criteria of a central scotoma on visual field testing and the use of magnifying aids to read. Examination included best-corrected visual acuity, magnification need, reading speed, and evaluation of fixation by corneal reflexes and by Rodenstock scanning laser ophthalmoscope (SLO). Central scotoma was assessed by conventional perimetry (Tübingen Automated Perimeter) and microperimetry (NIDEK MP1)., Results: Mean magnification need was 13.2 ± 7.3-fold (range: 2- to 25-fold). Mean reading speed was 53 ± 18 words per minute (WPM) (range: 24-85 WPM). With automated perimetry, all patients showed central scotomas with a mean radius of 13° ± 7° (range: 1°-30°) in the better eye. Microperimetry in all patients showed fenestrated central scotomas. Eccentric fixation with a preferred retinal locus (PRL) was detected with SLO examination and microperimetry correlated well in 11 of 12 patients. The SLO results showed no systematic pattern in the placement of the PRL; however, 7 of 12 patients (58%) placed their PRL in an unfavorable location left or below the fovea. In 8 of 12 patients, fixation was unstable. Between reading speed and central scotoma size, there was a statistically significant negative correlation (P = 0.021, r = -0.65)., Conclusions: The percentage of unfavorable PRL locations was extremely high compared with other disorders with central scotomas. Unstable fixation and fenestrated central scotomas led to difficulties in reading. Early rehabilitation and, if necessary, eccentric viewing training should be considered in LHON patients.

We present an 11-year-old girl with sudden, severe, sequential optic neuropathy. Investigations revealed severe vitamin B12 deficiency, and identified a novel mitochondrial ND5 variant. She was treated with steroids followed by plasma exchange, but the vision continued to deteriorate to eventual bilateral blindness over the next few months. Vitamin B12 deficiency can rarely cause severe irreversible visual loss secondary to optic neuropathy. The significance of the concurrent mitochondrial ND5 variant remains undetermined.