A case of neuromyelitis optica harboring both anti-aquaporin-4 antibodies and a pathogenic mitochondrial DNA mutation for Leber’s hereditary optic neuropathy

Shiraishi, Wataru; Hayashi, Shigenari; Kamada, Takashi; Isobe, Noriko; Yamasaki, Ryo; Murai, Hiroyuki; Ohyagi, Yasumasa; Kira, Jun Ichi

doi:10.1177/1352458513513057

Cited by 20 publications

(13 citation statements)

References 11 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our patient's episode of extensive spinal cord pathology could represent a separate coincidental issue, however; the coexistence of two relatively rare disorders seems particularly unlikely, given that numerous cases of apparent demyelination have been reported in LHON (Pfeffer et al 2013;Shiraishi et al 2014;Harding et al 1992;Parry-Jones et al 2008;Perez et al 2009). This syndrome, known as LHON-multiple sclerosis (LHON-MS), is essentially clini-cally and radiologically indistinguishable from multiple sclerosis, but with less ocular pain and a poorer visual prognosis (Pfeffer et al 2013;Matthews et al 2015).…”

Section: Discussionmentioning

confidence: 79%

Leber Hereditary Optic Neuropathy and Longitudinally Extensive Transverse Myelitis

et al. 2017

View full text Add to dashboard Cite

Leber Hereditary Optic Neuropathy is an inherited optic neuropathy caused by mitochondrial DNA point mutations leading to sudden, painless loss of vision. We report a case of an 8-year-old boy presenting with a radiological phenotype of longitudinally extensive transverse myelitis on a background of severe visual impairment secondary to Leber Hereditary Optic Neuropathy (LHON). He was found to have dual mitochondrial DNA mutations at 14484 (MTND6 gene) and 4160 (MTND1 gene) in a family with a severe form of LHON characterised by not only an unusually high penetrance of optic neuropathy, but also severe extra-ocular neurological complications. The m.14484T>C mutation is a common LHON mutation, but the m.4160T>C mutation is to our knowledge not reported outside this family and appears to drive the neurological manifestations. To our knowledge there have been no previous reports of spinal cord lesions in children with LHON.

show abstract

Section: Discussionmentioning

confidence: 79%

Leber Hereditary Optic Neuropathy and Longitudinally Extensive Transverse Myelitis

et al. 2017

View full text Add to dashboard Cite

show abstract

“…After decades of debate, clinicopathological studies have revealed striking differences between NMO and prototypic MS firmly establishing the two of them as distinct disease entities [23, 95, 113]. It is, therefore, interesting that in addition to Harding disease, patients with LHON have been described who developed a prominent spinal cord syndrome mimicking the radiological and pathological features of NMO [91, 122]. Additional research is clearly needed to further explore the interplay between a pathogenic LHON mutation, mitochondrial dysfunction and concurrent white matter CNS demyelinating disease [30, 85].…”

Section: Lhon Plus Phenotypesmentioning

confidence: 99%

A neurodegenerative perspective on mitochondrial optic neuropathies

et al. 2016

View full text Add to dashboard Cite

Mitochondrial optic neuropathies constitute an important cause of chronic visual morbidity and registrable blindness in both the paediatric and adult population. It is a genetically heterogeneous group of disorders caused by both mitochondrial DNA (mtDNA) mutations and a growing list of nuclear genetic defects that invariably affect a critical component of the mitochondrial machinery. The two classical paradigms are Leber hereditary optic neuropathy (LHON), which is a primary mtDNA disorder, and autosomal dominant optic atrophy (DOA) secondary to pathogenic mutations within the nuclear gene OPA1 that encodes for a mitochondrial inner membrane protein. The defining neuropathological feature is the preferential loss of retinal ganglion cells (RGCs) within the inner retina but, rather strikingly, the smaller calibre RGCs that constitute the papillomacular bundle are particularly vulnerable, whereas melanopsin-containing RGCs are relatively spared. Although the majority of patients with LHON and DOA will present with isolated optic nerve involvement, some individuals will also develop additional neurological complications pointing towards a greater vulnerability of the central nervous system (CNS) in susceptible mutation carriers. These so-called “plus” phenotypes are mechanistically important as they put the loss of RGCs within the broader perspective of neuronal loss and mitochondrial dysfunction, highlighting common pathways that could be modulated to halt progressive neurodegeneration in other related CNS disorders. The management of patients with mitochondrial optic neuropathies still remains largely supportive, but the development of effective disease-modifying treatments is now within tantalising reach helped by major advances in drug discovery and delivery, and targeted genetic manipulation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-016-1625-2) contains supplementary material, which is available to authorized users.

show abstract

“…[ 41 ] In a patient with LHON spinal cord lesions due to concomitant neuromyelitis optica (NMO) have been reported. [ 42 ] In patients with LHON and features of multiple sclerosis (MS), respectively NMO, it is conceivable that “demyelinating” lesions are in fact stroke-like lesions attributable to the MID with some clinical and instrumental features suggesting MS, respectively, NMO. In a patient with LHON and MS, new “inflammatory lesions” were seen on MRI of the brain and spinal cord 14 months after discontinuation of natalizumab.…”

Section: R Esultsmentioning

confidence: 99%

Involvement of the Spinal Cord in Mitochondrial Disorders

Finsterer

Zarrouk‐Mahjoub

2018

Journal of Neurosciences in Rural Practice

View full text Add to dashboard Cite

This review aims at summarising and discussing the current status concerning the clinical presentation, pathogenesis, diagnosis, and treatment of spinal cord affection in mitochondrial disorders (MIDs). A literature search using the database Pubmed was carried out by application of appropriate search terms and their combinations. Involvement of the spinal cord in MIDs is more frequent than anticipated. It occurs in specific and non-specific MIDs. Among the specific MIDs it has been most frequently described in LBSL, LS, MERRF, KSS, IOSCA, MIRAS, and PCH and only rarely in MELAS, CPEO, and LHON. Clinically, spinal cord involvement manifests as monoparesis, paraparesis, quadruparesis, sensory disturbances, hypotonia, spasticity, urinary or defecation dysfunction, spinal column deformities, or as transverse syndrome. Diagnosing spinal cord involvement in MIDs requires a thoroughly taken history, clinical exam, and imaging studies. Additionally, transcranial magnetic stimulation, somato-sensory-evoked potentials, and cerebro-spinal fluid can be supportive. Treatment is generally not at variance compared to the underlying MID but occasionally surgical stabilisation of the spinal column may be necessary. It is concluded that spinal cord involvement in MIDs is more frequent than anticipated but may be missed if cerebral manifestations prevail. Spinal cord involvement in MIDs may strongly determine the mobility of these patients.

show abstract

A case of neuromyelitis optica harboring both anti-aquaporin-4 antibodies and a pathogenic mitochondrial DNA mutation for Leber’s hereditary optic neuropathy

Cited by 20 publications

References 11 publications

Leber Hereditary Optic Neuropathy and Longitudinally Extensive Transverse Myelitis

Leber Hereditary Optic Neuropathy and Longitudinally Extensive Transverse Myelitis

A neurodegenerative perspective on mitochondrial optic neuropathies

Involvement of the Spinal Cord in Mitochondrial Disorders

Contact Info

Product

Resources

About