Neurol Sci (2004) 25:S380–S382 DOI 10.1007/s10072-004-0347-8
A. Ghezzi • S. Baldini • M. Zaffaroni • G. Leoni • T. Koudriavtseva • A.R. Casini • M. Zeviani
Devic’s neuromyelitis optica and mitochondrial DNA mutation: a case report
Abstract Cases are described with Leber’s optic atrophy and neurological symptoms and/or MRI lesions suggestive of multiple sclerosis. We describe a case of a young woman with Devic’s neuromyelitis optica and 3460 homoplasmic mitochondrial DNA mutation. Key words Leber’s optic atrophy • Devic’s neuromyelitis optica • Multiple sclerosis • Mitochondrial DNA mutation
Introduction Devic’s neuromyelitis optica (DNO) is a mono/polyphasic disease characterised by myelitis and optic neuritis in a single/recurrent attack, with no other concomitant neurological symptom. Criteria for diagnosis have been recently reviewed [1, 2], emphasising the role of brain (normal, at least in the initial stages of the disease) and spinal cord (lesions extending in more than 2 segments) magnetic resonance imaging (MRI). Cerebralspinal fluid (CSF) is a supportive criteria if it shows increased cell number or protein content. DNO is frequently associated to concomitant autoimmune diseases and is often preceded by infections or vaccination [1, 2]. We describe a case with DNO and concomitant mutation of mitochondrial DNA. To our knowledge, this is the first case with this association.
Case report
A. Ghezzi () • S. Baldini • M. Zaffaroni Centro Studi Sclerosi Multipla Ospedale di Gallarate Via Pastori 4, I-21013 Gallarate, Italy e-mail:
[email protected] G. Leoni U.O. Oculistica, Gallarate, Italy T. Koudriavtseva • A.R. Casini U.O. Neurologia, Ospedale S. Giovanni, Rome, Italy M. Zeviani Istituto Nazionale Neurologico C. Besta, Milan, Italy
A 26-year-old female, with a negative family history and no relevant previous diseases, presented an acute attack of left optic neuritis at 18 years of age. Visual acuity quickly dropped to 1/10 and, in spite of corticosteroid therapy, the impairment remained stable. Brain MRI was normal, and it was confirmed normal one year later. She was tested for mutation of mitochondrial DNA and resulted positive for 3460 mutation. Five years later, at age 25, she developed an acute optic neuritis in the right eye. Visual acuity was 4/10 in the right, 1/10 in the left eye. Brain MRI was again negative. Some months later she developed sensory and motor impairment in the lower limbs and urinary dysfunction. Spinal cord MRI showed two lesions, one at D8–D9 level, another at D11 level, with enhancement after Gadolinium administration. CSF showed a slight increase of cell number (10 WBC/mm3). Symptoms partially regressed but, on last examination (March 2004) mild sensory impairment in the
A. Ghezzi et al.: Devic’s neuromyelitis optica and mitochondrial DNA mutation
Healthy subject
Heteroplasmic mutation
right leg and urinary hesitance were observed. Visual acuity was 1/50 in the right eye, 1/10 in the left one. The family members were submitted to DNA analysis and results are shown in Figure 1.Visual acuity, visual field, visual evoked potentials were normal in all relatives, as well as neurological examination.
Homoplasmic mutation
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Fig. 1 Pedigree of the family. Arrow indicates index patient
To our knowledge, this is the first case presenting DNO and primary DNA mutation. Due to the rarity of the two disease, its casual association is unlike. As for MS, the role of DNA mutation is not clear and it will be interesting to extend such investigation to other subjects with DNO.
References Discussion In this case the diagnosis of DNO was supported by clinical data, consistent with subsequent involvement of the optic nerves and spinal cord. Brain MRI was normal, on the contrary spinal cord MRI revealed lesions in two different segments, one of them involving two segments. Diagnosis of DNO was further supported by the increase of CSF cells [1, 2]. This patient had DNA mutation, which was also discovered in heteroplasmic form in her mother, grand-mother and three uncles. The hypothesis that primary or secondary mutations of mitochondrial DNA may predispose to demyelinating diseases has been explored but not confirmed in MS. Primary mutations were absent in three groups of MS patients, and the frequency of secondary mutations was similar to that of controls [3–5]. Results have also been confirmed in familial cases of MS with maternal inheritance [6, 7]. On the contrary, after the study by Harding et al. [8] several cases were described with confirmed Leber’s optic atrophy and neurological symptoms and/or MRI lesions similar to those observed in definite MS [9–12, see ref. 13 for a review of studies up to 2000]. In these subjects, mitochondrial DNA mutation can contribute to sustaining lesions of the optic nerve but it is not clear what mechanism leads to the development of inflammatory-demyelinating lesions [6].
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