【摘要】 者，男性，马来人，26岁，以突发左眼视神经炎首诊，给予静脉甲基强的松龙治疗，3wk后完全缓解。1wk后，两次突发右眼视神经炎，Lhermitte 征和Uthoff 征呈阳性。第3d，患者双侧下身瘫痪，T8 水平感觉丧失，症状进行性恶化，至第5d患者卧床不起。MRI检查显示双侧视神经增宽，胸髓至腰髓、脑干及少量大脑半球可见多节段性长的脱髓鞘斑块。迅速给予静脉甲基强的松龙初始大剂量治疗，继而口服强的松龙，并且进行密切的神经理疗。3mo后患者康复，可以借助辅助行走器行走。7mo后患者完全康复，能够重新开始其网站联系人的工作。在随后的1a随访期，病情未复发，患者最终视力提高，右眼6/9，左眼6/6，右眼视野表现永久性轻度中心盲点性暗点和普遍性视敏度降低。
【关键词】 视神经脊髓炎；视神经炎；脊髓炎
INTRODUCTION
Neuromyelitis optica or Devics disease is an idiopathic demyelinating disease that selectively affect the optic nerves and spinal cord, typically spares the brain hemispheres, and generally follow a relapsing course[1]. It is characterized by the association of an acute or subacute demyelinating myelitis and unilateral or bilateral optic neuritis occurring in close temporal succession and resulting in paraplegia and blindness[2]. This rare syndrome is sometimes considered as a particular form of multiple sclerosis. Despite major progress in the past few years, the spectrum of neuromyelitis optica is still not fully understood,and difficult to distinguish it from multiple sclerosis, especially at first presentation which may only be an isolated optic neuritis or myelitis[3].
CASE REPORT
A 26 yearold Malay man presented with a sudden onset blurring of vision in the left eye and pain on eye movement. It was associated with headache, nausea and vomiting. There was no history of recent upper respiratory tract infection or sinusitis. His visual acuity was counting finger in the left eye and 6/6 in the right eye. Relative afferent pupillary defect (RAPD) was positive in the left eye. There were a reduced in brightness and colour vision. Fundoscopy revealed swollen and hyperaemic disc in the left eye (Figure 1A) however the right eye was normal. The Humphrey visual field demonstrated cecocentral scotoma with diffuse depression of sensitivity in the left eye (Figure 2A,B). MRI of brain and orbit showed enhancement and swollen optic nerve of the left eye (Figure 3). The brain hemisphere was normal. He was diagnosed to have left optic neuritis and was treated with intravenous methylprednisolone 250 mg QID for 3 days followed by oral prednisolone 1mg/kg per day for 11 days. The vision improved to 6/9 after 2 weeks. A month later, he presented again with a similar presentation in the right eye. He had an acute onset of poor vision of the right eye associated with pain on eye movement. He also complained of numbness and electrical sensation when he turned his head down, indicating positive Lhermitte sign. He also had Uhthoff phenomenon when he experienced poor vision during hot temperature or under hot sun. The visual acuity was non projection to light in the right eye and 6/9 in the left eye. RAPD was positive in the right eye. Fundoscopy revealed swollen and hyperaemic disc of the right eye (Figure 1B). The left disc however was normal and his general condition was stable. He was conscious and alert. All the vital signs were stable. There was no respiratory distress or any other neurological deficit. Patient was admitted to the ward for further investigations and treatment. On day3, he developed lower limbs weakness with motor power of 3/5 and also reduced sensation up to the level of T8. On day6, he was unable to pass urine and need to be catheterised. At the same period he also experienced erectile dysfunction. Other cranial nerves assessment and respiratory function were normal.
The erythrocyte sedimentation rate and C reactive protein were within normal limit. The VDRL, TPHA, herpes simplex virus serology and Retrovirus Elisa investigations were negative. He was screened for connective tissue disorder including rheumatoid factor, C3, C4, dsDNA, ANA, antiphopholipid antibody, antiLa antibody and antiRo antibody.
All the results were within normal limit. Patient refused lumbar puncture for cerebrospinal fluid analysis. Repeated MRI showed enhancement and swollen of the right optic nerve. There were few ill defined lesions seen in the left pons which extended superiorly to the left side of the midbrain. Other similar lesions were also seen in right medulla and right corona radiate. These lesions appeared hypointense on T1, hyperintense on T2, not suppressed on FLAIR and not enhanced on post gadolinium (Figure 4A). There were also patchy intramedullary ill defined lesions seen in the spinal cord at the cervical, thoracic and lumbar level which appear isointense on T1, hyperintense on T2 and sparing the brain hemisphere (Figure 4B). He was diagnosed to have neuromyelitis optica based on clinical features and MRI findings.
He was then promptly started on intravenous methylprednisolone 1g qid for 5 days and then continued with oral prednisolone 1mg/kg for another 4 weeks. He was on daily intensive neurophysiotherapy. About a month later, he developed left gluteal ulcer which showed a poor respond to the treatment. The gluteal ulcer was then successfully treated surgically with rotational fasciocutaneous flap. His general condition improved with treatment. He was able to walk with walking aids and having normal micturation after 3 months. He recovered fully after 7 months and started to work again. His visual acuity upon discharged was 6/36 in the right eye and 6/9 in the left eye and. He was followed up for 2 years and there was no relapse. His final visual acuity was improved to 6/9 in the right eye and 6/6 in the left eye. The Humphrey visual field showed persistent mild cecocentral scotoma and diffuse depression in sensitivity in the right eye, whereas the left eye was normal (Figure 2C,D).
DISCUSSION
The majority of patients with Devics disease are young with an mean age of 2527 years; and females outnumbered males by 1.8∶1 to 1.4∶1[4]. Devics disease generally manifests as an acute syndrome. Uingerchuk et al[2] reviewed 71 cases which showed the presence of a prodrome viral illness in 53% of the patients in the reviewed cases. This prodrome is characterized by headache, low grade fever, myalgia, fatigue and upper respiratory and gastrointestinal symptoms. Optic neuritis presents with a sudden and complete or partial loss of vision in a single eye, followed by a similar loss in the other eye within a few days. The myelitis of Devics disease manifests with parenthesis, gait difficulty and progressive weakening of the lower extremities[4]. The visual field defect in optic neuritis is cecocentral scotoma with diffuse depression in sensitivity, which is a characteristic of optic neuropathy visual field defect as demonstrated in this patient[5]. In qptic neuritis treatment trial, there was a greater number of abnormal visual field in the central static Humphrey visual field analyzer 302 compared to the peripheral kinetic Goldmann perimeter. The far periphery appears to recover faster and more complete when results from both Humphrey central static visual fields and Goldmann peripheral kinetic visual fields are compared. In majority of cases, the Humphrey visual field analyzer alone can effectively monitor the recovery of optic neuritis for the central visual fields. However, Goldmann peripheral kinetic visual field may provide additional data in cases with severe loss of central visual field[6].
The etiology of neuromyelitis optica remains unknown. The temporal association of the disease with infection has raised the possibility of an infectious etiology. Herpes simplex virus type 2 could induce demyelination of the optic nerve and spinal cord in the animal model. It was postulated that in adolescence and childhood, the spread of the infection was limited in these regions by a continuous presences of protective factor.
Neuromyelitis optica is also associated with autoimmune disordersa wide range of antibodies including antinuclear, antismooth muscle, Rh factor, anticardiolipin, antithyroid microsomal antibodies. These will cause Bcell dysregulation and complement activation which subsequently lead to demyelination, cavitations, necrosis in nerve tissue. Gliosis may be found in well developed nerve tissue lesions[4]. Antiphospholipid antibodies are found in a case of systemic lupus erythematosus with neuromyelitis optica, suggesting autoimmune disorder in this disease[7].
The distinction between neuromyelitis optica or Devic disease and multiple sclerosis has long been unclear. Neuromyelitis optica is believed to differ from multiple sclerosis by causing severe, often bilateral optic neuritis and longitudinally extensive MRI spinal cord lesions, but no MRI brain lesions[8]. Within 5 years of onset, 50% of patients are blind in both eyes and cannot walk unassisted, and 20% die of respiratory failure due to cervical myelitis , while in multiple sclerosis respiratory failure is virtually unknown[2]. CSF and MRI findings distinguish neuromyelitis optica from multiple sclerosis. Neutrophilic pleocytosis or >50 nucleated cells/mm3 in CSF was common in neuromyelitis optica but rare in multiple sclerosis. Oligoclonal bands, present in CSF in up to 90% of multiple sclerosis patients, were uncommon in neuromyelitis optica[1,2,9].
Wingerchuk et al[2] conducted a study of neuromyelitis optica in 93 patients from 1950 to 1993 at Mayo clinic. They proposed a diagnostic criteria for neuromyelitis optica based on absolute criteria, supportive major criteria and supportive minor criteria. The absolute criteria are optic neuritis, acute myelitis, and there is no evidence of clinical disease outside of the optic nerve or spinal cord. The major criteria are negative brain MRI at onset, spinal cord MRI with signal abnormality extending over ≥ 3 vertebra segments and, CSF pleocytosis of >50 WBC/mm3 or >5 neutrophils/mm3. The minor criteria are bilateral optic neuritis, severe optic neuritis with fixed visual acuity worse than 20/200 in at least one eye, and severe, fixed, attackedrelated weakness. The brain MRI signal abnormality is not typical for multiple sclerosis, that is, not involving the periventricular region and not scattered in the white matter. The diagnostic criteria requires all absolute criteria and one major criteria or two minor diagnostic criteria[2]. This patient met the diagnostic criteria having all the absolute criteria, two major and two minor criteria.
The issue of brain MRI lesions in neuromyelitis optica has been controversial. Rocca et al[10] added magnetization transfer and diffusion tensor sequences to conventional MRI in the examination of 10 patients with neuromyelitis optica and found the presence of tissue damage in areas where conventional T1 and T2 imaging showed no abnormalities. Pittock et al[11] conducted a study in 60 patients with neuromyelitis optica on the basis of Wingerchuks criteria and found 30 (50.0%) patients had normal MRI at the first onset of the disease. The subsequent followup MRI brain was normal in 14(23.3%) of the patients. The other 6 patients (10.0%) of the patients had subsequent MRI brain lesions including multiplesclerosis like lesion, nonspecific or atypical abnormalities. Thirty (30.0%) patients had abnormal multiplesclerosis, nonspecific or atypical brain MRI lesion.
In 2004, Lennon et al[1] found that NMOIgG test was positive in 73.0% of 45 patients with neuromyelitis optica, whereas only 9% of 22 multiple sclerosis patients were positive. NMOIgG were 73% sensitivity and 91% specificity for neuromyelitis optica. It was specific marker autoantibodies of neuromyelitis optica and binds at or near bloodbrain barrier antigen. It distinguishes neuromyelitis optica from multiple sclerosis. There was a role for autoantibody and local activation of complement for the pathogenesis of neuromyelitis optica. NMOIgG enables early diagnosis of neuromyelitis optica and immunosuppressive therapy, as well as monitor the progression and response to treatment. Various treatment options for neuromyelitis optica have been attempted, including intravenous steroids, immunosuppressive agents, and plasmapheresis.
Recently, encouraging results have been reported with plasma exchange, intravenous immunoglobulins, The intravenous methyprednisolone was given 250 mg qid for 3 days followed by oral prednisolone 60100mg for 23 weeks, and a slow taper over a 2month period. Some patients with recurrent Devics disease who have been treated with corticosteroids developed steroid dependency with sustained relapses on withdrawal of the steroid[4]. Mandler et al[12] in a prospective study, reported a beneficial effect of the combination of prednisolone and azathioprine. High doses of intravenous methylprednisolone 500mg twice daily for 5 days followed by oral prednisolone 1mg/kgperday for 2 months and slowly tapered to 10mg every 3 weeks with attempts to shift to an alternate day regime. At week 3 of prednisolone therapy, azathioprine 2mg/kg per day was added and given during the entire study period. During 18 months of treatment all patients responded positively and improved as their mean expanded disability (EDSS) score decreased from 8.2 to 4.0. The authors did not report any new relapses or new symptoms[4].
Minager et al[4] in one uncontrolled trial of prednisolone and methotrexate in patients with neuromyelitis optica reported successful stabilization of eight patients with a decrease in the EDSS score from 6.6 to 5.0 at 12 months, and 4.56 at 24 months. There was no relapse in these patients during 24 months follow up. There were other treatment options include lymphocytoplamapheresis,betainterferon and cyclophophamide. Supportive management with ventilator is mandatory in patients with respiratory centre involvement. WeinstockGuttman et al[13] conducted a prospective 2year study in five patients for treatment of neuromyelitis optica with mitoxantrone.Mitoxantrone is an anthracenedione antineoplastic agent for treatment worsening relapsing multiple sclerosis. Mitoxantrone potentially suppress Thelper lymphocytes and the humoral immune system via both macrophage and Bcell attenuation. They found improvement clinically and MRI images in 4 patients. In a study by Whitham et al[14],recurrences of neuromyelitis optica were reported to be 42%. The recurrences happened within 6 months in 55%, between 6 and 18 months in 27%, and after more than 5 years in 18% of the patients. In the same study, 58% of the patients remained relapsefree. Females had a higher recurrence rate than men.
【参考文献】
1 Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG. A serum autoantibody marker of neuromyelitis optica : distinction from multiple sclerosis. Lancet 2004;364(9451):21062112
2 Wingerchuk DM, Hogancamp WF, OBrien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devics syndrome). Neurology 1999;53(5):11071114
3 Weinshenker BG. Neuromyelitis optica : what it is and what it might be. Lancet 2003;361:889890
4 Minagar A, Alexander JS, Fowler MR, Long AC, Kelley RE.Devic disease: clinical course, pathophysiology, and management. Pathophysiology 2002;9(1):3340
5 Newman SA,Arnold AC.NeuroOphthalmology, in Basic and Clinical Science Course 2002.American Academy of Ophthalmology:San Francisco
6 Keltner JL, Johnson CA, Spurr JO, Beck RW. Comparison of central and peripheral visual field properties in the optic neuritis treatment trial.
Am J Ophthalmol 1999;128(5):543553
7 Charakidas A. Neuromyelitis optica (Devics disease) in a case of systemic lupus erythematosus with antiphospholipid antibodies: is there a role for anticoagulants? Neuro Ophthalmology 2004;28(4):179181
8 Cross SA.Rethinking neuromyelitis optica(Devic disease). J Neuroophthalmol 2007;27(1):5760
9 Zangemeister WH, MuellerJensen A. Neuromyelitis optica clinical and neurophysiological features. NeuroOphthalmology 1984;4(2):8188
10 Rocca MA, Agosta F, Mezzapesa DM, Martinelli V, Salvi F, Ghezzi A, Bergamaschi R, Comi G, Filippi M.Magnetization transfer and diffusion tensor MRI show gray matter damage in neuromyelitis optica. Neurology 2004;62(3): p.476478
11 Pittock SJ, Lennon VA, Krecke K, Wingerchuk DM, Lucchinetti CF, Weinshenker BG. Brain abnormalities in neuromyelitis optica. Arch
Neurol 2006;63(3):390396
12 Mandler RN, Ahmed W, Dencoff JE.Devics neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 1998;51(4):12191220
13 Guttman WB, Ramanathan M, Lincoff N, Napoli SQ, Sharma J, Feichter J, Bakshi R. Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease). Arch Neurol 2006;63(7):957963
14 Whitham RH, Brey RL. Neuromyelitis optica: two new cases and review of the literature. J Clin Neuroophthalmol 1985;5(4):263269
来源：首席医学网 |
