scholarly journals NI-19 A case of Leber’s hereditary optic neuropathy with diffuse white matter changes mimicking gliomatosis cerebri

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi21-vi21
Author(s):  
Wakiko Saruta ◽  
Ichiyo Shibahara ◽  
Madoka Inukai ◽  
Shunsuke Kanayama ◽  
Hisanao Akiyama ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Tissue ◽  
Optic Neuropathy ◽  
Vision Loss ◽  
Gliomatosis Cerebri ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
White Matter Changes ◽  
Diffuse White Matter ◽  
Hereditary Optic Neuropathy

Abstract BACKGROUND: Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The cranial magnetic resonance imaging (MRI) of LHON patients varies from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes. CASE REPORT: We report a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G>A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2’-deoxyguanosine positivity, suggesting the presence of oxidative stress. CONCLUSION: LHON is extremely difficult to diagnose unless we suspect or know the disease. The present case brings attention not only to LHON but other mtDNA mutated diseases that need to be considered with diffuse white matter changes or GC.

scholarly journals Leber’s hereditary optic neuropathy with diffuse white matter changes mimicking gliomatosis cerebri: illustrative case

2021 ◽  
Vol 1 (26) ◽  
Author(s):  
Wakiko Saruta ◽  
Ichiyo Shibahara ◽  
Hajime Handa ◽  
Madoka Inukai ◽  
Shunsuke Kanayama ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Tissue ◽  
Optic Neuropathy ◽  
Gliomatosis Cerebri ◽  
Illustrative Case ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
White Matter Changes ◽  
Diffuse White Matter ◽  
Hereditary Optic Neuropathy

BACKGROUIND Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The findings on cranial magnetic resonance imaging of patients with LHON vary from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes. OBSERVATIONS The authors reported a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity, supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G>A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2′-deoxyguanosine positivity, suggesting the presence of oxidative stress. LESSONS LHON is extremely difficult to diagnose unless one suspects or knows the disease. The present case brings attention not only to LHON but also to other mtDNA-mutated diseases that need to be considered with diffuse white matter changes or GC.

scholarly journals Neuroanatomical Changes in Leber’s Hereditary Optic Neuropathy: Clinical Application of 7T MRI Submillimeter Morphometry

2020 ◽  
Vol 10 (6) ◽  
pp. 359 ◽  
Author(s):  
Kamil Jonak ◽  
Paweł Krukow ◽  
Mark Symms ◽  
Ryszard Maciejewski ◽  
Cezary Grochowski
Keyword(s):  
White Matter ◽  
Optic Neuropathy ◽  
Clinical Picture ◽  
Diffusion Tensor ◽  
Optic Tract ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Lateral Ventricles ◽  
Subcortical Brain ◽  
Hereditary Optic Neuropathy

Leber’s hereditary optic neuropathy (LHON) is one of the mitochondrial diseases that causes loss of central vision, progressive impairment and subsequent degeneration of retinal ganglion cells (RGCs). In recent years, diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts, such as the optic tract, and optic radiation. However, it is still unclear if the disease alters only some parts of the white matter architecture or whether the changes also affect other subcortical areas of the brain. This study aimed to improve our understanding of morphometric changes in subcortical brain areas and their associations with the clinical picture in LHON by the application of a submillimeter surface-based analysis approach to the ultra-high-field 7T magnetic resonance imaging data. To meet these goals, fifteen LHON patients and fifteen age-matched healthy subjects were examined. For all individuals, quantitative analysis of the morphometric results was performed. Furthermore, morphometric characteristics which differentiated the groups were correlated with variables covering selected aspects of the LHON clinical picture. Compared to healthy controls (HC), LHON carriers showed significantly lower volume of both palladiums (left p = 0.023; right p = 0.018), the right accumbens area (p = 0.007) and the optic chiasm (p = 0.014). Additionally, LHON patients have significantly higher volume of both lateral ventricles (left p = 0.034; right p = 0.02), both temporal horns of the lateral ventricles (left p = 0.016; right p = 0.034), 3rd ventricle (p = 0.012) and 4th ventricle (p = 0.002). Correlation between volumetric results and clinical data showed that volume of both right and left lateral ventricles significantly and positively correlated with the duration of the illness (left R = 0.841, p = 0.002; right R = 0.755, p = 0.001) and the age of the LHON participants (left R = 0.656, p = 0.007; right R = 0.691, p = 0.004). The abnormalities in volume of the LHON patients’ subcortical structures indicate that the disease can cause changes not only in the white matter areas constituting visual tracts, but also in the other subcortical brain structures. Furthermore, the correlation between those results and the illness duration suggests that the disease might have a neurodegenerative nature; however, to fully confirm this observation, longitudinal studies should be conducted.

scholarly journals Mitochondrial DNA variation of Leber’s Hereditary Optic Neuropathy (LHON) in Western Siberia

2019 ◽  
Author(s):  
E.B. Starikovskaya ◽  
S.A. Shalaurova ◽  
S.V. Dryomov ◽  
A.M. Nazhmidenova ◽  
N.V. Volodko ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Optic Neuropathy ◽  
Western Siberia ◽  
Vision Loss ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Inherited Disease ◽  
Leber's Hereditary Optic Neuropathy ◽  
Mtdna Mutations ◽  
Pathogenic Mutations ◽  
Hereditary Optic Neuropathy

AbstractLeber’s hereditary optic neuropathy (LHON) is a form of disorder caused by pathogenic mutations in a mitochondrial DNA. LHON is maternally inherited disease, which manifests mainly in young adults, affecting predominantly males. Clinically LHON has a manifestation as painless central vision loss, resulting in early onset of disability. Epidemiology of LHON has not been fully investigated yet. In this study, we report 44 genetically unrelated families with LHON manifestation. We performed whole mtDNA genome sequencing and provided genealogical and molecular genetic data on mutations and haplogroup background of LHON patients in the Western Siberia population. Known “primary” pathogenic mtDNA mutations (MITOMAP) were found in 32 families: m.11778G>A represents 53,10% (17/32), m.3460G>A – 21,90% (7/32), m.14484T>C – 18,75% (6/32), and rare m.10663T>C and m.3635G>A represent 6,25% (2/32). We describe potentially pathogenic m.4659G>A in one subject without known pathogenic mutations, and potentially pathogenic m.9444C>T, m.6261G>A, m.9921G>A, m.8551T>C, m.8412T>C, m.15077G>A in families with known pathogenic mutations confirmed. We suppose these mutations could contribute to the pathogenesis of optic neuropathy development. Our results indicate that haplogroup affiliation and mutational spectrum of the Western Siberian LHON cohort substantially deviate from those of European populations.

scholarly journals Can the effects of the mitochondrial DNA mutations found in Leber’s hereditary optic neuropathy be protective against the development of cluster headache in smokers?

2020 ◽  
Vol 3 ◽  
pp. 251581632093957 ◽  
Author(s):  
Todd D Rozen
Keyword(s):  
Mitochondrial Dna ◽  
Cluster Headache ◽  
Protective Effect ◽  
Optic Neuropathy ◽  
Vision Loss ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Tobacco Exposure ◽  
Mtdna Mutations ◽  
Hereditary Optic Neuropathy

Is it possible that some mitochondrial DNA (mtDNA) mutations enhance the risk of developing a headache disorder while other mutations actually confer a protective effect? Mitochondrial disorders have been linked to migraine but very rarely to cluster headache (CH). The true pathogenesis of CH is unknown but a linkage to cigarette smoking is irrefutable. Leber’s hereditary optic neuropathy is a syndrome of bilateral vision loss that typically manifests in a patient’s 20s and 30s, is male predominant, and its sufferers are heavy smokers and heavy drinkers. Tobacco exposure is so linked to the condition that only smokers appear to develop vision loss while nonsmokers remain unaffected carriers of their mutations. In essence, the Leber’s hereditary optic neuropathy population is the CH population but at present there have been no reported cases of CH in this mitochondrial subgroup. Thus, could the effects of the mtDNA mutations found in Leber’s hereditary optic neuropathy, which involve complex I of the electron transport chain, actually confer a protective effect against the development of CH? This article will delve into this theory.

scholarly journals Leber’s hereditary optic neuropathy misdiagnosed as optic neuritis and Lyme disease in a patient with multiple sclerosis

2018 ◽  
Vol 11 (1) ◽  
pp. e227109 ◽  
Author(s):  
Melinda Chang
Keyword(s):  
Multiple Sclerosis ◽  
Optic Neuritis ◽  
Optic Disc ◽  
Optic Neuropathy ◽  
Vision Loss ◽  
White Matter Lesions ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Intravenous Steroids ◽  
Hereditary Optic Neuropathy

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.

White Matter Changes in Two Leber's Hereditary Optic Neuropathy Pedigrees: 12-Year Follow-Up

2015 ◽  
Vol 235 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Jasna Jančić ◽  
Ivana Dejanović ◽  
Saša Radovanović ◽  
Jelena Ostojić ◽  
Duško Kozić ◽  
...  
Keyword(s):  
White Matter ◽  
Magnetic Resonance ◽  
Optic Neuropathy ◽  
Cerebellar Hemisphere ◽  
Resonance Spectroscopy ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Leber's Hereditary Optic Neuropathy ◽  
Mitochondrial Dna Mutation ◽  
Dna Mutation ◽  
Hereditary Optic Neuropathy

We are presenting two Leber's hereditary optic neuropathy (LHON) pedigrees with abnormal magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) findings but without neurological manifestation associated with LHON. The study included 14 LHON patients and 41 asymptomatic family members from 12 genealogically unrelated families. MRI showed white matter involvement and H-MRS exhibited metabolic anomalies within 12 LHON families. Main outcome measures were abnormal MRI and H-MRS findings in two pedigrees. MRI of the proband of the first pedigree showed a single demyelinating lesion in the right cerebellar hemisphere, while the proband of the second family displayed multiple supratentorial and infratentorial lesions, compatible with the demyelinating process, and both the absolute choline (Cho) concentration and Cho/creatinine ratio were increased. MRI and H-MRS profiles of both affected and unaffected mitochondrial DNA mutation carriers suggest more widespread central nervous involvement in LHON. Although even after 12 years our patients did not develop neurological symptoms, MRI could still be used to detect possible changes during the disease progression.

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