- Email: [email protected]
Neuromyelitis optica: what it is and what it might be
COMMENTARY
Raj N Kalaria Institute for Ageing and Health, Wolfson Unit, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK (e-mail: [email protected]) 1
2 3
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5 6
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9
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WHO. Active ageing: a policy framework. Geneva: WHO, 2002: http://www.who.int/hpr/ageing/ActiveAgeingPolicyFrame.pdf (accessed Feb 21, 2003). Baxter J. Mail’s 125-year-old woman. Dec 5, 2002: http://news.bbc.co. uk/1/hi/world/africa/2543879.stm (accessed on Feb 21, 2003). Kalaria RN, Skoog I. Overlap with Alzheimer’s disease. In: Erkinjuntti T, Gauthier S. Vascular cognitive impairment. London: Martin Dunitz, 2002: 145–66. Hofman A, Ott A, Breteler MMB, et al. Atherosclerosis, apolipoprotein E, and the prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. Lancet 1997; 349: 151–54. Ruitenberg A, van Swieten JC, Witteman JC, et al. Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet 2002; 359: 281–86. Ott A, Breteler MM, van Harskamp F, et al. Prevalence of Alzheimer’s disease and vascular dementia: association with education: the Rotterdam study. BMJ 1995; 310: 970–73. Burmeister LA, Ganguli M, Dodge HH, et al. Hypothyroidism and cognition: preliminary evidence for a specific defect in memory. Thyroid 2001; 11: 1177–85. WHO. World Health Organization: process for a global strategy on diet, physical activity and health. Geneva: WHO, February, 2003: http://www. who.int/hpr/NPH/docs/GlobalStretegy.pdf (accessed Feb 21, 2003). Hendrie HC, Osuntokun BO, Hall KS, et al. Prevalence of Alzheimer’s disease and dementia in two communities: Nigerian Africans and African Americans. Am J Psychiatry 1995; 152: 1485–92. Chandra V, Ganguli M, Pandav R, et al. Prevalence of Alzheimer’s disease and other dementias in rural India: the Indo-US study. Neurology 1998; 51: 1000–08. Hendrie HC, Ogunniyi AO, Hall KS, et al. Incidence of dementia and Alzheimer’s disease in 2 communities: Yoruba residing in Ibadan, Nigeria and African-Americans residing in Indianapolis, Indiana. JAMA 2001; 285: 739–47. Chandra V, Pandav R, Dodge HH, et al. Incidence of Alzheimer’s disease in a rural community in India: the Indo-US study. Neurology 2001; 57: 985–89. Zhang M, Katzman R, Yu E, Liu W, Xiao SF, Yan H. A preliminary analysis of incidence of dementia in Shanghai, China. Psychiatry Clin Neurosci 1998 52 (suppl): S291–94. Kalaria RN, Ogeng’o JA, Patel NB, et al. Evaluation of risk factors for Alzheimer’s disease in elderly East Africans. Brain Res Bull 1997; 44: 573–77. Farrag A, Farwiz HM, Khedr EH, et al. Prevalence of Alzheimer’s disease and other dementing disorders: Assiut-Upper Egypt study. Dement Geriatr Cogn Disord 1998; 9: 323–28. Bowirrat A, Treves TA, Friedland RP, et al. Prevalence of Alzheimer’s type dementia in an elderly Arab population. Eur J Neurol 2001; 8: 119–23.
Neuromyelitis optica: what it is and what it might be The nosology of the idiopathic inflammatory demyelinating diseases of the central nervous system remains confusing.1 One subtype of relapsing-remitting demyelinating disease, neuromyelitis optica (Devic’s disease), has recently been recognised as distinct from prototypic multiple sclerosis, despite the fact that most patients with neuromyelitis optica have a relapsing-remitting course and satisfy diagnostic criteria for multiple sclerosis.2,3 Neuromyelitis optica used to be thought of as a monophasic disease characterised by bilateral optic neuritis and myelitis occurring in rapid succession, on the basis of a case reported by Devic.4 Japanese investigators have not restricted the diagnosis of neuromyelitis optica to patients with monophasic disease.5 Although recognising that neuromyelitis optica is commonly a relapsing condition, they have distinguished neuromyelitis optica from classic or western multiple sclerosis by referring to it as Asian or opticospinal variant of multiple sclerosis. Relapsing neuromyelitis optica has generally been misclassified as multiple sclerosis in the west, which is a major although
THE LANCET • Vol 361 • March 15, 2003 • www.thelancet.com
probably not the sole factor explaining the differences in frequency of neuromyelitis optica in Asia versus the west. Experience with 71 patients at the Mayo Clinic2 confirmed that most cases of neuromyelitis optica in the USA have a relapsing course and can be distinguished from multiple sclerosis on the basis of key features (panel). Asian and African ancestries are common, but most North American patients are white. Restricting the diagnosis on the basis of an arbitrary interval between events or by requiring bilateral rather than unilateral involvement of optic nerves precludes full appreciation of the spectrum of the disorder. Some presentations are not consistent with neuromyelitis optica, such as chronic progressive myelopathy without acute attacks of previous myelitis, even in the presence of optic neuropathy and a negative scan of the head by MRI; primary progressive multiple sclerosis is more likely to be the diagnosis in this setting. No one criterion is specific for neuromyelitis optica, and a scoring system of major and minor criteria, similar to that for many rheumatological diseases, is necessary for accurate diagnosis.2 Is the clinical picture sufficiently specific to distinguish neuromyelitis optica from multiple sclerosis? One approach to address this question is to study the most typical cases, and exclude those whose condition overlaps with multiple sclerosis, such as those who have parenchymal lesions on MRI of the brain. Using this approach in examining cases of pure opticospinal variant of multiple sclerosis in Japan, T Misu and colleagues7 find that 31% of 118 patients with multiple sclerosis had opticospinal variant of multiple sclerosis, but only 9% satisfied criteria for pure opticospinal variant of multiple sclerosis (normal magnetic resonance scan of the head, apart from optic nerve abnormalities, on repeated examination, and 5 or more years of follow-up). The characteristics of the pure subgroup were similar to those reported in other series of neuromyelitis optica. The patients were mostly female (90%), had cord lesions extending over three or more vertebral segments (80%), and lacked oligoclonal IgG bands in cerebrospinal fluid (100%). Misu and colleagues did not find a positive association with the HLA-DPB1*0501 allele or a negative association with DRB1*1501, the allele associated with multiple sclerosis in the west.8,9 However, the sample size was too small to be definitive and HLA-DPB1*0501 tended to be overrepresented in the most severely affected cases. The cases reported in Misu’s study almost certainly have neuromyelitis optica. However, Misu’s criteria and our proposed diagnostic criteria2 might include patients with optic neuritis, myelitis, and negative magnetic resonance scan of the head who may ultimately prove to have multiple sclerosis on follow-up. The most specific finding for neuromyelitis optica is a longitudinally extensive, central, gadolinium-enhancing lesion in the cord on MRI in the setting of myelitis, which is very rare in multiple sclerosis. Demographic and clinical characteristics of opticospinal variant of multiple sclerosis in Japan and relapsing neuromyelitis optica in the west are sufficiently similar to suggest that they are identical. Whilst Misu and colleagues7 point out that some of their cases had milder attacks than reported in western series, we have also observed mild attacks in white patients, although attacks are generally severer in neuromyelitis optica than in multiple sclerosis. Is the spectrum of neuromyelitis optica broader than initially suspected? Patients with negative magnetic resonance scans of the head who have recurrent optic neuritis but never myelitis, or who have recurrent myelitis but never optic neuritis, could be examples of patients with a fragment of neuromyelitis optica. Some patients with longitudinally extensive myelitis highly typical of that seen in neuromyelitis optica have abnormal visual evoked potentials, 889
For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
Comparison of neuromyelitis optica and multiple scelorosis Course Distribution Attack severity Respiratory failure MRI head MRI cord CSF cells CSF oligoclonal bands Permanent disability Female Coexistent autoimmune disease Pathology6
Neuromyelitis optica Monophasic or relapsing Optic nerves and spinal cord only Usually severe 30% of cases due to cervical myelitis Usually normal or non-specific Multiple, small, peripheral lesions
Multiple sclerosis Relapsing Any white-matter tract Usually mild Rarely if ever Multiple periventricular white-matter lesions Longitudinally extensive, central necrotic lesions; may cause syrinx
Occasional pleocytosis (>50 white cells per L) during attacks; may have polymorphonuclear cells Usually absent Usually attack-related 80–90% Frequent (30–50%)
Rarely >25 white cells per L; all mononuclear Usually present Usually in late progressive phase 60–70% Uncommon
T cells, B cells and macrophages; prominent necrosis; eosinophilic and neutrophilic infiltrate prominent; vascular proliferation and hyalinisation; complement activation in perivascular rosette pattern
T cells, B cells and macrophages; variable degree of necrosis; neutrophilic infiltrate rare; complement activation less marked and present in <50% cases
CSF=cerebrospinal fluid.
suggesting that they may have a disorder within the neuromyelitis optica spectrum,10 even though standard clinical criteria require both clinically manifest optic neuritis and myelitis. Progressive necrotic myelopathy might be a variant of neuromyelitis optica with exclusive spinal-cord involvement.11 Patients with classic autoimmune diseases, including systemic lupus erythematosus12 and Sjögren’s syndrome,13 can develop neuromyelitis optica. Should they be regarded as having neuromyelitis optica or neurological complications of a systemic autoimmune disease? The distinction between neuromyelitis optica, multiple sclerosis, and neurological complications of a systemic autoimmune disease may seem semantic, but has therapeutic implications. Treatment with antiplatelet and anticoagulant drugs has been recommended for neuromyelitis optica in the presence of anticardiolipin antibodies,14 invoking possible vascular mechanisms. Are these antibodies pathogenic and as such an indication for intervention? Or are they merely a reflection of polyclonal B-cell activation that is not organ specific? Because patients with neuromyelitis optica have an excellent response to plasma exchange when steroid therapy fails,15 this therapeutic option may merit earlier consideration in patients with neuromyelitis optica with severe clinical attacks. Azathioprine is generally regarded as the treatment of choice to suppress attacks of neuromyelitis optica,16 whereas interferon beta or glatiramer acetate are treatments of choice for multiple sclerosis. Despite major progress over the past 5 years, the spectrum of neuromyelitis optica is not fully understood, nor can it be distinguished from multiple sclerosis, especially at first presentation with isolated optic neuritis or myelitis. There are no specific biological markers for multiple sclerosis or neuromyelitis optica. Discovery of such a marker would enormously advance clinical diagnosis and research into these diseases. Brian G Weinshenker Mayo Clinic/Mayo Foundation, Rochester, MN 55902, USA (e-mail: [email protected]) 1
2
3
Weinshenker BG, Miller D. MS: One disease or many? In: Siva A, Kesselring J, Thompson A, eds. Frontiers in multiple sclerosis. London: Martin Dunitz, 1999: 37–46. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 1999; 53: 1107–14. de Seze J, Stojkovic T, Ferriby D, et al. Devic’s neuromyelitis optica: clinical, laboratory, MRI and outcome profile. J Neurolog Sci 2002; 197: 57–61.
890
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13 14
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Devic C. Myelite subaigue compliquee de neurite optique. Bull Med 1894; 35: 18–30. Kuroiwa Y. Clinical and epidemiological aspects of multiple sclerosis in Japan. Jap J Med 1982; 21: 135–40. Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain 2002; 125: 1450–61. Misu T, Fujihara K, Nakashima I, et al. Pure optic-spinal form of multiple sclerosis in Japan. Brain 2002; 125: 2460–68. Ono T, Zambenedetti MR, Yamasaki K, et al. Molecular analysis of HLA class I (HLA-A and -B) and HLA class II (HLA-DRB1) genes in Japanese patients with multiple sclerosis (Western type and Asian type). Tiss Antigens 1998; 52: 539–42. Yamasaki K, Horiuchi I, Minohara M, et al. HLA-DPB1*0501associated opticospinal multiple sclerosis: clinical, neuroimaging and immunogenetic studies. Brain 1999; 122: 1689–96. Masuhr F, Busch M, Wetzel K, Harms L, Schielke E. Relapsing myelitis with pathological visual evoked potentials: a case of neuromyelitis optica? Eur J Neurol 2002; 9: 430–32. Katz JD, Ropper AH. Progressive necrotic myelopathy: clinical course in 9 patients. Arch Neurol 2000; 57: 355–61. Bonnet F, Mercie P, Morlat P, et al. Devic’s neuromyelitis optica during pregnancy in a patient with systemic lupus erythematosus. Lupus 1999; 8: 244–47. Mochizuki A, Hayashi A, Hisahara S, Shoji S. Steroid-responsive Devic’s variant in Sjogren’s syndrome. Neurology 2000; 54: 1391–92. Karussis D, Leker RR, Ashkenazi A, Abramsky O. A subgroup of multiple sclerosis patients with anticardiolipin antibodies and unusual clinical manifestations: do they represent a new nosological entity? Ann Neurol 1998; 44: 629–34. Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2002; 58: 143–46. Mandler RN, Ahmed W, Dencoff JE. Devic’s neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 1998; 51: 1219–20.
Human metapneumovirus in the community In their recent report,1 J Stockton and colleagues identify the recently discovered human metapneumovirus (hMPV) in 1·3% of patients with influenza-like illness in the UK. About a year ago hMPV was discovered in young children with acute respiratory illness ranging from mild upper respiratory tract disease to severe bronchiolitis and pneumonia.2 On the basis of virological data, sequence homology, and gene constellation, the virus was characterised as the first mammalian member of the recently assigned genus Metapneumovirus, of which avian pneumovirus was the sole member until then.2,3 Serological studies in the Netherlands had shown that by the age of 5 years virtually all children had been infected with hMPV at least once and that the virus has
THE LANCET • Vol 361 • March 15, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Raj N Kalaria Institute for Ageing and Health, Wolfson Unit, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, UK (e-mail: [email protected]) 1
2 3
4
5 6
7
8
9
10
11
12
13
14
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WHO. Active ageing: a policy framework. Geneva: WHO, 2002: http://www.who.int/hpr/ageing/ActiveAgeingPolicyFrame.pdf (accessed Feb 21, 2003). Baxter J. Mail’s 125-year-old woman. Dec 5, 2002: http://news.bbc.co. uk/1/hi/world/africa/2543879.stm (accessed on Feb 21, 2003). Kalaria RN, Skoog I. Overlap with Alzheimer’s disease. In: Erkinjuntti T, Gauthier S. Vascular cognitive impairment. London: Martin Dunitz, 2002: 145–66. Hofman A, Ott A, Breteler MMB, et al. Atherosclerosis, apolipoprotein E, and the prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. Lancet 1997; 349: 151–54. Ruitenberg A, van Swieten JC, Witteman JC, et al. Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet 2002; 359: 281–86. Ott A, Breteler MM, van Harskamp F, et al. Prevalence of Alzheimer’s disease and vascular dementia: association with education: the Rotterdam study. BMJ 1995; 310: 970–73. Burmeister LA, Ganguli M, Dodge HH, et al. Hypothyroidism and cognition: preliminary evidence for a specific defect in memory. Thyroid 2001; 11: 1177–85. WHO. World Health Organization: process for a global strategy on diet, physical activity and health. Geneva: WHO, February, 2003: http://www. who.int/hpr/NPH/docs/GlobalStretegy.pdf (accessed Feb 21, 2003). Hendrie HC, Osuntokun BO, Hall KS, et al. Prevalence of Alzheimer’s disease and dementia in two communities: Nigerian Africans and African Americans. Am J Psychiatry 1995; 152: 1485–92. Chandra V, Ganguli M, Pandav R, et al. Prevalence of Alzheimer’s disease and other dementias in rural India: the Indo-US study. Neurology 1998; 51: 1000–08. Hendrie HC, Ogunniyi AO, Hall KS, et al. Incidence of dementia and Alzheimer’s disease in 2 communities: Yoruba residing in Ibadan, Nigeria and African-Americans residing in Indianapolis, Indiana. JAMA 2001; 285: 739–47. Chandra V, Pandav R, Dodge HH, et al. Incidence of Alzheimer’s disease in a rural community in India: the Indo-US study. Neurology 2001; 57: 985–89. Zhang M, Katzman R, Yu E, Liu W, Xiao SF, Yan H. A preliminary analysis of incidence of dementia in Shanghai, China. Psychiatry Clin Neurosci 1998 52 (suppl): S291–94. Kalaria RN, Ogeng’o JA, Patel NB, et al. Evaluation of risk factors for Alzheimer’s disease in elderly East Africans. Brain Res Bull 1997; 44: 573–77. Farrag A, Farwiz HM, Khedr EH, et al. Prevalence of Alzheimer’s disease and other dementing disorders: Assiut-Upper Egypt study. Dement Geriatr Cogn Disord 1998; 9: 323–28. Bowirrat A, Treves TA, Friedland RP, et al. Prevalence of Alzheimer’s type dementia in an elderly Arab population. Eur J Neurol 2001; 8: 119–23.
Neuromyelitis optica: what it is and what it might be The nosology of the idiopathic inflammatory demyelinating diseases of the central nervous system remains confusing.1 One subtype of relapsing-remitting demyelinating disease, neuromyelitis optica (Devic’s disease), has recently been recognised as distinct from prototypic multiple sclerosis, despite the fact that most patients with neuromyelitis optica have a relapsing-remitting course and satisfy diagnostic criteria for multiple sclerosis.2,3 Neuromyelitis optica used to be thought of as a monophasic disease characterised by bilateral optic neuritis and myelitis occurring in rapid succession, on the basis of a case reported by Devic.4 Japanese investigators have not restricted the diagnosis of neuromyelitis optica to patients with monophasic disease.5 Although recognising that neuromyelitis optica is commonly a relapsing condition, they have distinguished neuromyelitis optica from classic or western multiple sclerosis by referring to it as Asian or opticospinal variant of multiple sclerosis. Relapsing neuromyelitis optica has generally been misclassified as multiple sclerosis in the west, which is a major although
THE LANCET • Vol 361 • March 15, 2003 • www.thelancet.com
probably not the sole factor explaining the differences in frequency of neuromyelitis optica in Asia versus the west. Experience with 71 patients at the Mayo Clinic2 confirmed that most cases of neuromyelitis optica in the USA have a relapsing course and can be distinguished from multiple sclerosis on the basis of key features (panel). Asian and African ancestries are common, but most North American patients are white. Restricting the diagnosis on the basis of an arbitrary interval between events or by requiring bilateral rather than unilateral involvement of optic nerves precludes full appreciation of the spectrum of the disorder. Some presentations are not consistent with neuromyelitis optica, such as chronic progressive myelopathy without acute attacks of previous myelitis, even in the presence of optic neuropathy and a negative scan of the head by MRI; primary progressive multiple sclerosis is more likely to be the diagnosis in this setting. No one criterion is specific for neuromyelitis optica, and a scoring system of major and minor criteria, similar to that for many rheumatological diseases, is necessary for accurate diagnosis.2 Is the clinical picture sufficiently specific to distinguish neuromyelitis optica from multiple sclerosis? One approach to address this question is to study the most typical cases, and exclude those whose condition overlaps with multiple sclerosis, such as those who have parenchymal lesions on MRI of the brain. Using this approach in examining cases of pure opticospinal variant of multiple sclerosis in Japan, T Misu and colleagues7 find that 31% of 118 patients with multiple sclerosis had opticospinal variant of multiple sclerosis, but only 9% satisfied criteria for pure opticospinal variant of multiple sclerosis (normal magnetic resonance scan of the head, apart from optic nerve abnormalities, on repeated examination, and 5 or more years of follow-up). The characteristics of the pure subgroup were similar to those reported in other series of neuromyelitis optica. The patients were mostly female (90%), had cord lesions extending over three or more vertebral segments (80%), and lacked oligoclonal IgG bands in cerebrospinal fluid (100%). Misu and colleagues did not find a positive association with the HLA-DPB1*0501 allele or a negative association with DRB1*1501, the allele associated with multiple sclerosis in the west.8,9 However, the sample size was too small to be definitive and HLA-DPB1*0501 tended to be overrepresented in the most severely affected cases. The cases reported in Misu’s study almost certainly have neuromyelitis optica. However, Misu’s criteria and our proposed diagnostic criteria2 might include patients with optic neuritis, myelitis, and negative magnetic resonance scan of the head who may ultimately prove to have multiple sclerosis on follow-up. The most specific finding for neuromyelitis optica is a longitudinally extensive, central, gadolinium-enhancing lesion in the cord on MRI in the setting of myelitis, which is very rare in multiple sclerosis. Demographic and clinical characteristics of opticospinal variant of multiple sclerosis in Japan and relapsing neuromyelitis optica in the west are sufficiently similar to suggest that they are identical. Whilst Misu and colleagues7 point out that some of their cases had milder attacks than reported in western series, we have also observed mild attacks in white patients, although attacks are generally severer in neuromyelitis optica than in multiple sclerosis. Is the spectrum of neuromyelitis optica broader than initially suspected? Patients with negative magnetic resonance scans of the head who have recurrent optic neuritis but never myelitis, or who have recurrent myelitis but never optic neuritis, could be examples of patients with a fragment of neuromyelitis optica. Some patients with longitudinally extensive myelitis highly typical of that seen in neuromyelitis optica have abnormal visual evoked potentials, 889
For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
Comparison of neuromyelitis optica and multiple scelorosis Course Distribution Attack severity Respiratory failure MRI head MRI cord CSF cells CSF oligoclonal bands Permanent disability Female Coexistent autoimmune disease Pathology6
Neuromyelitis optica Monophasic or relapsing Optic nerves and spinal cord only Usually severe 30% of cases due to cervical myelitis Usually normal or non-specific Multiple, small, peripheral lesions
Multiple sclerosis Relapsing Any white-matter tract Usually mild Rarely if ever Multiple periventricular white-matter lesions Longitudinally extensive, central necrotic lesions; may cause syrinx
Occasional pleocytosis (>50 white cells per L) during attacks; may have polymorphonuclear cells Usually absent Usually attack-related 80–90% Frequent (30–50%)
Rarely >25 white cells per L; all mononuclear Usually present Usually in late progressive phase 60–70% Uncommon
T cells, B cells and macrophages; prominent necrosis; eosinophilic and neutrophilic infiltrate prominent; vascular proliferation and hyalinisation; complement activation in perivascular rosette pattern
T cells, B cells and macrophages; variable degree of necrosis; neutrophilic infiltrate rare; complement activation less marked and present in <50% cases
CSF=cerebrospinal fluid.
suggesting that they may have a disorder within the neuromyelitis optica spectrum,10 even though standard clinical criteria require both clinically manifest optic neuritis and myelitis. Progressive necrotic myelopathy might be a variant of neuromyelitis optica with exclusive spinal-cord involvement.11 Patients with classic autoimmune diseases, including systemic lupus erythematosus12 and Sjögren’s syndrome,13 can develop neuromyelitis optica. Should they be regarded as having neuromyelitis optica or neurological complications of a systemic autoimmune disease? The distinction between neuromyelitis optica, multiple sclerosis, and neurological complications of a systemic autoimmune disease may seem semantic, but has therapeutic implications. Treatment with antiplatelet and anticoagulant drugs has been recommended for neuromyelitis optica in the presence of anticardiolipin antibodies,14 invoking possible vascular mechanisms. Are these antibodies pathogenic and as such an indication for intervention? Or are they merely a reflection of polyclonal B-cell activation that is not organ specific? Because patients with neuromyelitis optica have an excellent response to plasma exchange when steroid therapy fails,15 this therapeutic option may merit earlier consideration in patients with neuromyelitis optica with severe clinical attacks. Azathioprine is generally regarded as the treatment of choice to suppress attacks of neuromyelitis optica,16 whereas interferon beta or glatiramer acetate are treatments of choice for multiple sclerosis. Despite major progress over the past 5 years, the spectrum of neuromyelitis optica is not fully understood, nor can it be distinguished from multiple sclerosis, especially at first presentation with isolated optic neuritis or myelitis. There are no specific biological markers for multiple sclerosis or neuromyelitis optica. Discovery of such a marker would enormously advance clinical diagnosis and research into these diseases. Brian G Weinshenker Mayo Clinic/Mayo Foundation, Rochester, MN 55902, USA (e-mail: [email protected]) 1
2
3
Weinshenker BG, Miller D. MS: One disease or many? In: Siva A, Kesselring J, Thompson A, eds. Frontiers in multiple sclerosis. London: Martin Dunitz, 1999: 37–46. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 1999; 53: 1107–14. de Seze J, Stojkovic T, Ferriby D, et al. Devic’s neuromyelitis optica: clinical, laboratory, MRI and outcome profile. J Neurolog Sci 2002; 197: 57–61.
890
4 5 6
7 8
9
10
11 12
13 14
15
16
Devic C. Myelite subaigue compliquee de neurite optique. Bull Med 1894; 35: 18–30. Kuroiwa Y. Clinical and epidemiological aspects of multiple sclerosis in Japan. Jap J Med 1982; 21: 135–40. Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain 2002; 125: 1450–61. Misu T, Fujihara K, Nakashima I, et al. Pure optic-spinal form of multiple sclerosis in Japan. Brain 2002; 125: 2460–68. Ono T, Zambenedetti MR, Yamasaki K, et al. Molecular analysis of HLA class I (HLA-A and -B) and HLA class II (HLA-DRB1) genes in Japanese patients with multiple sclerosis (Western type and Asian type). Tiss Antigens 1998; 52: 539–42. Yamasaki K, Horiuchi I, Minohara M, et al. HLA-DPB1*0501associated opticospinal multiple sclerosis: clinical, neuroimaging and immunogenetic studies. Brain 1999; 122: 1689–96. Masuhr F, Busch M, Wetzel K, Harms L, Schielke E. Relapsing myelitis with pathological visual evoked potentials: a case of neuromyelitis optica? Eur J Neurol 2002; 9: 430–32. Katz JD, Ropper AH. Progressive necrotic myelopathy: clinical course in 9 patients. Arch Neurol 2000; 57: 355–61. Bonnet F, Mercie P, Morlat P, et al. Devic’s neuromyelitis optica during pregnancy in a patient with systemic lupus erythematosus. Lupus 1999; 8: 244–47. Mochizuki A, Hayashi A, Hisahara S, Shoji S. Steroid-responsive Devic’s variant in Sjogren’s syndrome. Neurology 2000; 54: 1391–92. Karussis D, Leker RR, Ashkenazi A, Abramsky O. A subgroup of multiple sclerosis patients with anticardiolipin antibodies and unusual clinical manifestations: do they represent a new nosological entity? Ann Neurol 1998; 44: 629–34. Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2002; 58: 143–46. Mandler RN, Ahmed W, Dencoff JE. Devic’s neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 1998; 51: 1219–20.
Human metapneumovirus in the community In their recent report,1 J Stockton and colleagues identify the recently discovered human metapneumovirus (hMPV) in 1·3% of patients with influenza-like illness in the UK. About a year ago hMPV was discovered in young children with acute respiratory illness ranging from mild upper respiratory tract disease to severe bronchiolitis and pneumonia.2 On the basis of virological data, sequence homology, and gene constellation, the virus was characterised as the first mammalian member of the recently assigned genus Metapneumovirus, of which avian pneumovirus was the sole member until then.2,3 Serological studies in the Netherlands had shown that by the age of 5 years virtually all children had been infected with hMPV at least once and that the virus has
THE LANCET • Vol 361 • March 15, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.