Neuromyelitis optica and neuromyelitis optica spectrum disorders have been recently associated with the disease-specific autoantibody aquaporin-4, thought to be pathogenic. Identifying this antibody has allowed the clinical phenotype to be broadened. It is clear that some patients with similar clinical features do not have this antibody and may have a different condition with different outcomes and prognosis. Previous clinical neuromyelitis optica and neuromyelitis optica spectrum disorder studies have included such patients. We investigated clinical outcomes and prognostic characteristics of 106 aquaporin-4 antibody-seropositive patients from the UK and Japan. We looked at predictors of disability outcomes, namely visual disability (permanent bilateral visual loss with visual acuity of <6/36 in the best eye), motor disability (permanent inability to walk further than 100 m unaided), wheelchair dependence and mortality. Data were collected largely retrospectively through review of case records. After median disease duration of 75 months, 18% had developed permanent bilateral visual disability, 34% permanent motor disability, 23% had become wheelchair dependent and 9% had died. Age at disease onset appeared to be an important predictor of disability type. Young-onset patients in the UK, but not the Japanese cohort, commonly presenting with optic neuritis, had a high risk of visual disability while older patients in both cohorts had a high risk of motor disability, regardless of their onset symptom. Genetic factors also appeared important. The UK cohort seemed to have more severe disease than the Japanese cohort, with more severe onset attacks, a higher relapse frequency and greater disability at follow-up, despite earlier immunosuppression. Moreover, within the UK cohort, there were important differences between ethnic groups, with Afro-Caribbean patients having a younger age at disease onset, more brain and multifocal attacks and higher likelihood of visual disability than Caucasian patients. Thus, age at disease onset and genetic factors are both likely to be important in determining clinical outcomes in aquaporin-4 disease. This has important implications for interpreting clinical neuromyelitis optica and neuromyelitis optica spectrum disorder studies, since clinical features and outcomes appear not to be generic across populations and may need to be tailored to individual groups. These factors need to be explored further in future prospective neuromyelitis optica and neuromyelitis optica spectrum disorder studies.

We used the Kaplan-Meier product limit method to estimate rates and Cox proportional hazards regression analysis with bootstrap validation to model significant independent predictors of and temporal trends in survival and recurrent stroke among 1,111 residents of Rochester, MN, who had a first cerebral infarction from 1975 through 1989. The risk of death after first cerebral infarction was 7% +/- 0.7% at 7 days, 14% +/- 1.0% at 30 days, 27% +/- 1.3% at 1 year, and 53% +/- 1.5% at 5 years. Independent risk factors for death after first cerebral infarction were age (p< 0.0001), congestive heart failure (p < 0.0001), persistent atrial fibrillation (p < 0.0001), recurrent stroke (p < 0.0001), and ischemic heart disease (p < 0.0001 for age < or =70, p > 0.05 for age >70). The risk of recurrent stroke after first cerebral infarction was 2% +/- 0.4% at 7 days, 4% +/- 0.6% at 30 days, 12% +/- 1.1% at 1 year, and 29% +/- 1.7% at 5 years. Age (p = 0.0002) and diabetes mellitus (p = 0.0004) were the only significant independent predictors of recurrent stroke. Neither the year nor the quinquennium of the first cerebral infarction was a significant determinant of survival or recurrence. The temporal trend toward improving survival after first cerebral infarction documented in Rochester, MN, in the decades before 1975 has ended.

Objectives:To determine the risk factors and incidence of cerebral infarction associated with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome. Methods:The Mayo Clinic dysproteinemia database was queried to identify patients with coded diagnosis of POEMS syndrome. Patients with cerebral infarction, occurring after the onset of POEMS-related symptoms, were selected. A retrospective observational study design was used to evaluate potential predictors of stroke in patients with POEMS syndrome.Results: A total of 9 patients (10%; 95% confidence interval 5.4 -17.9) with cerebral infarction were identified (2 women, 22%). Traditional stroke risk factors were not significantly different between the stroke and nonstroke subgroups, but hematologic abnormalities such as elevated platelet count and bone marrow plasmacytosis differed between the 2 groups. Cerebral infarction occurrence after successful treatment of the underlying condition was not observed. CT and MRI data demonstrated a wide spectrum of infarct topography in these patients. Common stroke etiologies comprised suspected vascular structural abnormalities leading to vessel dissection and stenosis, in addition to embolism from a proximal source.

AZA is a modestly effective treatment for NMO. However, many patients discontinue AZA over time and this seems to reflect poor tolerability more than lack of efficacy.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a rare paraneoplastic syndrome, caused by a plasma cell proliferative disorder, which is most commonly lambda restricted. The neurological hallmark, which forms one of the mandatory criteria for diagnosis, is a subacute onset demyelinating neuropathy, which can be rapidly disabling and painful. A number of multi-system features are also characteristic of this disorder, and certainly not restricted to those included in its acronym, which though limited, remains a useful and memorable name, helping distinguish POEMS syndrome from other paraproteinaemic neuropathies. The discovery of vascular endothelial growth factor (VEGF) in association with POEMS syndrome has been extremely useful in aiding clinical diagnosis, and monitoring response to treatment, as well as helping understand the underlying mechanism of disease. Interestingly, however, treatment targeting VEGF has been disappointing, suggesting other disease mechanisms or inflammatory processes are also important. Current understanding of the pathogenesis of POEMS syndrome is outlined in detail in the accompanying article by Cerri et al. Here, we review the clinical features of POEMS syndrome, differential diagnosis and available treatment options, based on current literature.

IntroductionNeuromyelitis optica (NMO) is a severe inflammatory condition causing optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM). Limited forms are called NMO spectrum disorder (NMOSD). Pathogenic aquaporin-4 (AQP4) antibodies are found in most patients with NMO and some with NMOSD. Previous studies have included seronegative patients in their cohorts despite suggestions that they may behave differently. Ethnic differences have not previously been directly studied.MethodsWe compared the clinical features and early long-term prognostic characteristics of 106 AQP4 antibody positive NMO/NMOSD patients from the UK (n=59) and Japan (n=47).ResultsOnset age was similar in both cohorts. The majority of both cohorts experienced a relapsing course but relapse rates were higher in the UK cohort. Attacks of LETM resulted in greater disability in the UK cohort. Motor disability was greater in those with late onset disease and in Caucasians, whatever their onset symptom. Visual disability was worse in young onset patients presenting with ON. Early treatment appeared to be associated with reduced visual disability in both cohorts and reduced motor disability only in the Japanese cohort. The small number of males in the UK cohort did worse than females.ConclusionNMO appears to be more severe in Caucasians than in Asians but outcome is also influenced by onset age, gender and treatment.

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