Clinical approach to optic neuropathies

Raed Behbehani, Raed Behbehani

Abstract

Optic neuropathy is a frequent cause of vision loss encountered by ophthalmologist. The diagnosis is made on clinical grounds. The history often points to the possible etiology of the optic neuropathy. A rapid onset is typical of demyelinating, inflammatory, ischemic and traumatic causes. A gradual course points to compressive, toxic/nutritional and hereditary causes. The classic clinical signs of optic neuropathy are visual field defect, dyschromatopsia, and abnormal papillary response. There are ancillary investigations that can support the diagnosis of optic neuropathy. Visual field testing by either manual kinetic or automated static perimetry is critical in the diagnosis. Neuro-imaging of the brain and orbit is essential in many optic neuropathies including demyelinating and compressive. Newer technologies in the evaluation of optic neuropathies include multifocal visual evoked potentials and optic coherence tomography.

Keywords: Leber’s optic neuropathy; arteritic anterior ischemic optic neuropathy (AION); dominant optic atrophy; multiple sclerosis; non-arteritic anterior ischemic optic neuropathy (NAION); optic neuritis; optic neuropathy; optical coherence tomography; radiation optic neuropathy; recessive optic atrophy; traumatic optic neuropathy.

Figures

Figure 1
Figure 1
(A) Axial MRI of the brain (FLAIR sequence) showing the classic periventricular white matter lesions seen in MS. (B) Sagittal MRI showing peri-collosal white matter lesions also known as “Dawson’s fingers”.
Figure 2
Figure 2
An 11 year old boy with sudden onset of visual loss 2 weeks following a viral upper respiratory tract infection. Bilateral disc swelling was seen in the right (A) and left (B) disc. Visual acuity improved over 1 week spontaneously from counting fingers to 20/20 in both eyes.
Figure 3
Figure 3
A 57 year old patient with history of hypertension, diabetes and hypercholesterolemia and NAION in his right eye. There is pallid swelling of the right disc with hemorrhage superiorly. The left optic disc has a cup to disc ratio of 0.1 (not shown).
Figure 4
Figure 4
Disc swelling in GCA. Note pallid disc swelling with hemorrhages and an adjacent area of choroidal infarction (arrow) (courtesy of Peter J Savino, MD).
Figure 5
Figure 5
A 55 year old women with chronic disc swelling and optic neuropathy in the right eye. MRI showed enhancement of the intracranial nerve. An extensive work up, including a spinal tap, was negative. An optic nerve sheath biopsy showed optic nerve lymphoma with no systemic involvement.
Figure 6
Figure 6
An axial contrast-enhanced MRI of the orbit showing enhancement of the intra-orbital and intra-canalicular optic nerve in a lady with optic nerve sheath meningioma in the right eye.
Figure 7
Figure 7
A 55 year old lady carrier of the 3460 G LHON mitochondrial mutation, with bilateral disc swelling (top figure). Automated 24–2 perimetry (middle figure) shows bilateral arcuate defects and 10–2 perimetry shows bilateral central scotomas (bottom figure). The patient is a carrier the 3460 G LHON mitochondrial mutation.

References

    1. Ajax ET, Kardon R. Late-onset Leber’s hereditary optic neuropathy. J Neuroophthalmol. 1998;18:30–1.
    1. Ajlouni K, Jarrah N, et al. Wolfram syndrome: identification of a phenotypic and genotypic variant from Jordan. Am J Med Genet. 2002;115:61–5.
    1. Arnold AC. Evolving management of optic neuritis and multiple sclerosis. Am J Ophthalmol. 2005;139:1101–8.
    1. Arnold AC, Hepler RS. Natural history of nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 1994;14:66–9.
    1. Asproudis IC, Nikas AN, et al. Paraneoplastic optic neuropathy in a patient with a non-small cell lung carcinoma: a case report. Eur J Ophthalmol. 2005;15:420–3.
    1. Atkins EJ, Biousse V, et al. The natural historyof optic neuritis. Rev Neurol Dis. 2006;3:45–56.
    1. Bangsgaard R, Larsen VA, et al. Isolated bilateral optic neuritis in acute disseminated encephalomyelitis. Acta Ophthalmol Scand. 2006;84:815–7.
    1. Barboni P, Savini G, et al. Retinal nerve fiber layer evaluation by optical coherence tomography in Leber’s hereditary optic neuropathy. Ophthalmology. 2005;112:120–6.
    1. Barbosa AP, Carvalho D, et al. Inefficiency of the anticoagulant therapy in the regression of the radiation-induced optic neuropathy in Cushing’s disease. J Endocrinol Invest. 1999;22:301–5.
    1. Beck RW. The optic neuritis treatment trial: three-year follow-up results. Arch Ophthalmol. 1995;113:136–7.
    1. Beck RW, Chandler DL, et al. Interferon beta-1a for early multiple sclerosis: CHAMPS trial subgroup analyses. Ann Neurol. 2002;51:481–90.
    1. Beck RW, Trobe JD, et al. High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial. Arch Ophthalmol. 2003;121:944–9.
    1. Behbehani R, Mathews MK, et al. Nonarteritic anterior ischemic optic neuropathy in patients with sleep apnea while being treated with continuous positive airway pressure. Am J Ophthalmol. 2005;139:518–21.
    1. Behbehani RS, Vacarezza N, et al. Isolated optic nerve lymphoma diagnosed by optic nerve biopsy. Am J Ophthalmol. 2005;139:1128–30.
    1. Belden CJ, Hamed LM, et al. Bilateral isolated retrobulbar optic neuropathy in limited Wegener’s granulomatosis. J Clin Neuroophthalmol. 1993;13:119–23.
    1. Bianchi-Marzoli S, Rizzo JF, 3rd, et al. Quantitative analysis of optic disc cupping in compressive optic neuropathy. Ophthalmology. 1995;102:436–40.
    1. Blakely EL, de Silva R, et al. LHON/MELAS overlap syndrome associated with a mitochondrial MTND1 gene mutation. Eur J Hum Genet. 2005;13:623–7.
    1. Boschetti M, De Lucchi M, et al. Partial visual recovery from radiation-induced optic neuropathy after hyperbaric oxygen therapy in a patient with Cushing disease. Eur J Endocrinol. 2006;154:813–8.
    1. Bower SP, Hawley I, et al. Cardiac arrhythmia and Leber’s hereditary optic neuropathy. Lancet. 1992;339:1427–8.
    1. Brazis PW, Liesegang TJ, et al. When do optic disc edema and peripheral neuropathy constitute poetry? Surv Ophthalmol. 1990;35:219–25.
    1. Brittain GP, McIlwaine GG, et al. Plasma viscosity or erythrocyte sedimentation rate in the diagnosis of giant cell arteritis? Br J Ophthalmol. 1991;75:656–9.
    1. Brown GC, Shields JA, et al. Leukemic optic neuropathy. Int Ophthalmol. 1981;3:111–16.
    1. Buono LM, Foroozan R, et al. Heparin therapy in giant cell arteritis. Br J Ophthalmol. 2004;88:298–301.
    1. Buono LM, Foroozan R, et al. Posterior ischemic optic neuropathy after hemodialysis. Ophthalmology. 2003;110:1216–8.
    1. Burde RM. Optic disk risk factors for nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 1993;116:759–64.
    1. Cabre P, Heinzlef O, et al. MS and neuromyelitis optica in Martinique (French West Indies) Neurology. 2001;56:507–14.
    1. Calvert PC. A CR(I)MP in the optic nerve: recognition and implications of paraneoplastic optic neuropathy. J Neuroophthalmol. 2006;26:165–7.
    1. Clare G, Colley S, et al. Reversible optic neuropathy associated with low-dose methotrexate therapy. J Neuroophthalmol. 2005;25:109–12.
    1. Costello F, Coupland S, et al. Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol. 2006;59:963–9.
    1. Costello F, Zimmerman MB, et al. Role of thrombocytosis in diagnosis of giant cell arteritis and differentiation of arteritic from non-arteritic anterior ischemic optic neuropathy. Eur J Ophthalmol. 2004;14:245–57.
    1. Danesh-Meyer HV, Savino PJ, et al. Low diagnostic yield with second biopsies in suspected giant cell arteritis. J Neuroophthalmol. 2000;20:213–5.
    1. Danesh-Meyer HV, Savino PJ, et al. The prevalence of cupping in end-stage arteritic and nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 2001;108:593–8.
    1. Danesh-Meyer HV, Savino PJ, et al. Visual loss despite anticoagulation in radiation-induced optic neuropathy. Clin Experiment Ophthalmol. 2004;32:333–5.
    1. Das S, Bendok BR, et al. 2006Return of vision after transarterial coiling of a carotid cavernous sinus fistula: case report Surg Neurol 6682–5.discussion 85.
    1. De Palma P, Franco F, et al. The incidence of optic neuropathy in 84 patients treated with ethambutol. Metab Pediatr Syst Ophthalmol. 1989;12:80–2.
    1. Deramo VA, Sergott RC, et al. 2003Ischemic optic neuropathy as the first manifestation of elevated cholesterol levels in young patients Ophthalmology 1101041–6.discussion 1046.
    1. DeVita EG, Miao M, et al. Optic neuropathy in ethambutol-treated renal tuberculosis. J Clin Neuroophthalmol. 1987;7:77–86.
    1. Fay AM, Kane SA, et al. Magnetic resonance imaging of optic perineuritis. J Neuroophthalmol. 1997;17:247–9.
    1. Feldon SE. Anterior ischemic optic neuropathy: trouble waiting to happen. Ophthalmology. 1999;106:651–2.
    1. Francois J. [Hereditary optic atrophies] J Genet Hum. 1976;24:183–200.
    1. Fraser CL, Klistorner A, et al. Multifocal visual evoked potential analysis of inflammatory or demyelinating optic neuritis. Ophthalmology. 2006;113:323 e1–323 e2.
    1. Frohman L, Turbin R, et al. Autoimmune optic neuropathy with anticardiolipin antibody mimicking multiple sclerosis in a child. Am J Ophthalmol. 2003;136:358–60.
    1. Godel V, Nemet P, et al. Chloramphenicol optic neuropathy. Arch Ophthalmol. 1980;98:1417–21.
    1. Golnik KC, Schaible ER. Folate-responsive optic neuropathy. J Neuroophthalmol. 1994;14:163–9.
    1. Gropman A, Chen TJ, et al. Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation. Am J Med Genet A. 2004;124:377–82.
    1. Guy J, Mancuso A, et al. 1990Gadolinium-DTPA-enhanced magnetic resonance imaging in optic neuropathies Ophthalmology 97592–9.discussion 599–600.
    1. Han SH, Lee OY, et al. [A case of optic neuritis associated with Crohn’s disease] Korean J Gastroenterol. 2006;48:42–5.
    1. Haupert CL, Newman NJ. Prolonged Uhthoff phenomenon in sarcoidosis. Am J Ophthalmol. 1997;124:564–6.
    1. Hayreh SS. Role of nocturnal arterial hypotension in the development of ocular manifestations of systemic arterial hypertension. Curr Opin Ophthalmol. 1999;10:474–82.
    1. Hayreh SS. Posterior ischaemic optic neuropathy: clinical features, pathogenesis, and management. Eye. 2004;18:1188–206.
    1. Hayreh SS, Podhajsky PA, et al. Giant cell arteritis: validity and reliability of various diagnostic criteria. Am J Ophthalmol. 1997;123:285–96.
    1. Hayreh SS, Podhajsky PA, et al. Occult giant cell arteritis: ocular manifestations. Am J Ophthalmol. 1998a;125:521–6.
    1. Hayreh SS, Podhajsky PA, et al. Ocular manifestations of giant cell arteritis. Am J Ophthalmol. 1998b;125:509–20.
    1. Hayreh SS, Podhajsky PA, et al. Ipsilateral recurrence of non-arteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 2001;132:734–42.
    1. Hayreh SS, Zimmerman B. Visual deterioration in giant cell arteritis patients while on high doses of corticosteroid therapy. Ophthalmology. 2003;110:1204–15.
    1. Hou LC, Murphy MA. Traumatic optic neuropathy caused by a merchandise display hook. J Pediatr Ophthalmol Strabismus. 2004;41:249–50.
    1. Houshmand M, Mahmoudi T, et al. Identification of a new human mtDNA polymorphism (A14290G) in the NADH dehydrogenase subunit 6 gene. Braz J Med Biol Res. 2006;39:725–30.
    1. Hoyt CS. Autosomal dominant optic atrophy. A spectrum of disability. Ophthalmology. 1980;87:245–51.
    1. Hsu CT, Miller NR, et al. Optic neuropathy from folic acid deficiency without alcohol abuse. Ophthalmologica. 2002;216:65–7.
    1. Jabs DA, Miller NR, et al. Optic neuropathy in systemic lupus erythematosus. Arch Ophthalmol. 1986;104:564–8.
    1. Jiang RS, Hsu CY, et al. Endoscopic optic nerve decompression for the treatment of traumatic optic neuropathy. Rhinology. 2001;39:71–4.
    1. Kansu T, Kirkali P, et al. Optic neuropathy in Behcet’s disease. J Clin Neuroophthalmol. 1989;9:277–80.
    1. Katz BJ, Zhao Y, et al. A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4–Xp11.2. Am J Med Genet A. 2006;140:2207–11.
    1. Kerrison JB. Latent, acute, and chronic Leber’s hereditary optic neuropathy. Ophthalmology. 2005;112:1–2.
    1. Kidd D, Burton B, et al. Chronic relapsing inflammatory optic neuropathy (CRION) Brain. 2003;126:276–84.
    1. Kline LB, Kim JY, et al. Radiation optic neuropathy. Ophthalmology. 1985;92(8):1118–26.
    1. Kupersmith MJ, Burde RM, et al. Autoimmune optic neuropathy: evaluation and treatment. J Neurol Neurosurg Psychiatry. 1988;51:1381–6.
    1. Lee AG, Lin DJ, et al. Atypical features prompting neuroimaging in acute optic neuropathy in adults. Can J Ophthalmol. 2000;35:325–30.
    1. Lennon VA, Wingerchuk DM, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364:2106–12.
    1. Lessell S. Friendly fire: neurogenic visual loss from radiation therapy. J Neuroophthalmol. 2004;24:243–50.
    1. Levin LA, Beck RW, et al. The treatment of traumatic optic neuropathy: the International Optic Nerve Trauma Study. Ophthalmology. 1999;106:1268–77.
    1. Lim ET, Sellebjerg F, et al. Acute axonal damage predicts clinical outcome in patients with multiple sclerosis. Mult Scler. 2005;11:532–6.
    1. Lincoff NS, Erlich PD, et al. Thrombocytosis in temporal arteritis rising platelet counts: a red flag for giant cell arteritis. J Neuroophthalmol. 2000;20:67–72.
    1. Liu GT, Glaser JS, et al. Visual morbidity in giant cell arteritis. Clinical characteristics and prognosis for vision. Ophthalmology. 1994;101:1779–85.
    1. Lucchinetti CF, Kiers L, et al. Risk factors for developing multiple sclerosis after childhood optic neuritis. Neurology. 1997;49:1413–8.
    1. Luiz JE, Lee AG, et al. Paraneoplastic optic neuropathy and autoantibody production in small-cell carcinoma of the lung. J Neuroophthalmol. 1998;18:178–81.
    1. Manchester PT, Jr, Calhoun FP., Jr Dominant hereditary optic atrophy with bitemporal field defects. AMA Arch Ophthalmol. 1958;60:479–84.
    1. McCulley TJ, Lam BL, et al. A comparison of risk factors for postoperative and spontaneous nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2005;25:22–4.
    1. Medeiros FA, Moura FC, et al. Axonal loss after traumatic optic neuropathy documented by optical coherence tomography. Am J Ophthalmol. 2003;135:406–8.
    1. Mojon DS, Hedges TR, 3rd, et al. Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol. 2002;120:601–5.
    1. Murakami T, Mita S, et al. Hereditary cerebellar ataxia with Leber’s hereditary optic neuropathy mitochondrial DNA 11778 mutation. J Neurol Sci. 1996;142:111–3.
    1. Murphy MA. Bilateral posterior ischemic optic neuropathy after lumbar spine surgery. Ophthalmology. 2003;110:1454–7.
    1. Murphy MA, Murphy JF. Amiodarone and optic neuropathy: the heart of the matter. J Neuroophthalmol. 2005;25:232–6.
    1. Nakamura M, Yamamoto M. Variable pattern of visual recovery of Leber’s hereditary optic neuropathy. Br J Ophthalmol. 2000;84:534–5.
    1. Nakashima I, Fujihara K, et al. Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG. J Neurol Neurosurg Psychiatry. 2006;77:1073–5.
    1. Newman NJ. Hereditary optic neuropathies: from the mitochondria to the optic nerve. Am J Ophthalmol. 2005;140:517–23.
    1. Newman NJ, Scherer R, et al. The fellow eye in NAION: report from the ischemic optic neuropathy decompression trial follow-up study. Am J Ophthalmol. 2002;134:317–28.
    1. Nishi T, Ueda T, et al. Traumatic optic neuropathy caused by blunt injury to the inferior orbital rim. J Neuroophthalmol. 2006;26:44–6.
    1. Palombi K, Renard E, et al. Non-arteritic anterior ischaemic optic neuropathy is nearly systematically associated with obstructive sleep apnoea. Br J Ophthalmol. 2006;90:879–82.
    1. Parikh M, Miller NR, et al. Prevalence of a normal C-reactive protein with an elevated erythrocyte sedimentation rate in biopsy-proven giant cell arteritis. Ophthalmology. 2006;113:1842–5.
    1. Paulus W, Straube A, et al. Central nervous system involvement in Leber’s optic neuropathy. J Neurol. 1993;240:251–3.
    1. Pianka P, Almog Y, et al. Hyperhomocystinemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion. Ophthalmology. 2000;107:1588–92.
    1. Pittock SJ, Lennon VA, et al. Brain abnormalities in neuromyelitis optica. Arch Neurol. 2006;63:390–6.
    1. Pless M, Rizzo JF, 3rd, et al. Concordance of bilateral temporal artery biopsy in giant cell arteritis. J Neuroophthalmol. 2000;20:216–8.
    1. Pro MJ, Pons ME, et al. Imaging of the optic disc and retinal nerve fiber layer in acute optic neuritis. J Neurol Sci. 2006;250:114–9.
    1. Purvin V, Kawasaki A, et al. Optic neuropathy in patients using amiodarone. Arch Ophthalmol. 2006;124:696–701.
    1. Rajiniganth MG, Gupta AK, et al. Traumatic optic neuropathy: visual outcome following combined therapy protocol. Arch Otolaryngol Head Neck Surg. 2003;129:1203–6.
    1. Riordan-Eva P, Sanders MD, et al. The clinical features of Leber’s hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain. 1995;118:319–37.
    1. Rizzo JF, 3rd, Lessell S. Tobacco amblyopia. Am J Ophthalmol. 1993;116:84–7.
    1. Rubiera M, Rio J, et al. Neuromyelitis optica diagnosis in clinically isolated syndromes suggestive of multiple sclerosis. Neurology. 2006;66:1568–70.
    1. Sadda SR, Nee M, et al. Clinical spectrum of posterior ischemic optic neuropathy. Am J Ophthalmol. 2001;132:743–50.
    1. Sadun AA, Martone JF, et al. Epidemic optic neuropathy in Cuba. Eye findings. Arch Ophthalmol. 1994;112:691–9.
    1. Salvarani C, Hunder GG. Giant cell arteritis with low erythrocyte sedimentation rate: frequency of occurence in a population-based study. Arthritis Rheum. 2001;45:140–5.
    1. Savini G, Bellusci C, et al. Detection and quantification of retinal nerve fiber layer thickness in optic disc edema using stratus OCT. Arch Ophthalmol. 2006;124:1111–7.
    1. Sergott RC, Cohen MS, et al. Optic nerve decompression may improve the progressive form of nonarteritic ischemic optic neuropathy. Arch Ophthalmol. 1989;107:1743–54.
    1. Sheorajpanday R, Slabbynck H, et al. Small cell lung carcinoma presenting as collapsin response-mediating protein (CRMP)-5 paraneoplastic optic neuropathy. J Neuroophthalmol. 2006;26:168–72.
    1. Shimada Y, Shibuya M, et al. Bilateral optic neuropathy associated with multiple myeloma. J Neuroophthalmol. 2006;26:117–20.
    1. Spoor TC, McHenry JG, et al. Progressive and static nonarteritic ischemic optic neuropathy treated by optic nerve sheath decompression. Ophthalmology. 1993;100:306–11.
    1. Steinsapir KD. Treatment of traumatic optic neuropathy with high-dose corticosteroid. J Neuroophthalmol. 2006;26:65–7.
    1. Thambisetty MR, Scherzer CR, et al. Paraneoplastic optic neuropathy and cerebellar ataxia with small cell carcinoma of the lung. J Neuroophthalmol. 2001;21:164–7.
    1. Trip SA, Schlottmann PG, et al. Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann Neurol. 2005;58:383–91.
    1. Trip SA, Schlottmann PG, et al. Optic nerve atrophy and retinal nerve fibre layer thinning following optic neuritis: evidence that axonal loss is a substrate of MRI-detected atrophy. Neuroimage. 2006;31:286–93.
    1. Trobe JD, Glaser JS, et al. Nonglaucomatous excavation of the optic disc. Arch Ophthalmol. 1980a;98:1046–50.
    1. Trobe JD, Glaser JS, et al. Optic atrophy. Differential diagnosis by fundus observation alone. Arch Ophthalmol. 1980b;98:1040–5.
    1. Tsai RK, Lee YH. Reversibility of ethambutol optic neuropathy. J Ocul Pharmacol Ther. 1997;13:473–7.
    1. Tsai RK, Liu YT, et al. Risk factors of non-arteritic anterior ischemic optic neuropathy (NAION): ocular or systemic. Kaohsiung J Med Sci. 1998;14:221–5.
    1. van Oostenbrugge RJ, Twijnstra A. Presenting features and value of diagnostic procedures in leptomeningeal metastases. Neurology. 1999;53:382–5.
    1. Vaphiades MS, Newman NJ. Optic nerve enhancement on orbital magnetic resonance imaging in Leber’s hereditary optic neuropathy. J Neuroophthalmol. 1999;19:238–9.
    1. Votruba M. Molecular genetic basis of primary inherited optic neuropathies. Eye. 2004;18:1126–32.
    1. Walter SH, Bertz H, et al. Bilateral optic neuropathy after bone marrow transplantation and cyclosporin A therapy. Graefes Arch Clin Exp Ophthalmol. 2000;238:472–6.
    1. Wang MY, Arnold AC, et al. Bilateral blindness and lumbosacral myelopathy associated with high-dose carmustine and cisplatin therapy. Am J Ophthalmol. 2000;130:367–8.
    1. Watanabe M, Mita S, et al. Leber’s hereditary optic neuropathy with dystonia in a Japanese family. J Neurol Sci. 2006;243:31–4.
    1. Weisfeld-Adams JD, Dutton GN, et al. Vincristine sulfate as a possible cause of optic neuropathy. Pediatr Blood Cancer 2005
    1. Wilejto M, Shroff M, et al. The clinical features, MRI findings, and outcome of optic neuritis in children. Neurology. 2006;67:258–62.
    1. Wingerchuk DM, Lennon VA, et al. Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006;66:1485–9.
    1. Wise CM, Agudelo CA. Optic neuropathy as an initial manifestation of Sjogren’s syndrome. J Rheumatol. 1988;15:799–802.
    1. Wohlrab TM, Maas S, et al. Surgical decompression in traumatic optic neuropathy. Acta Ophthalmol Scand. 2002;80:287–93.
    1. Yu Z, Kryzer TJ, et al. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001;49:146–54.
    1. Zhadanov SI, Atamanov VV, et al. A novel mtDNA ND6 gene mutation associated with LHON in a Caucasian family. Biochem Biophys Res Commun. 2005;332(4):1115–21.

Source: PubMed

3
订阅