BackgroundThe diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.ObjectiveTo analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.MethodsRetrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).ResultsSeropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.ConclusionThis study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.

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Background: The prospective, multinational European ‘Stroke in Young Fabry Patients' (sifap1) study collected 4,467 patients with acute ischemic cerebrovascular events aged 18-55 years. Initially, aetiologic subtyping was performed using the TOAST classification; however, recently the phenotypic ASCO classification was presented and might be more useful to identify stroke aetiologies in young patients with a wide set of different causes. ASCO is a classification system divided in four etiologic categories (Atherosclerosis, Small vessel disease (SVD), Cardiac embolism, Other cause) with different grades of severity (1-3) and aims to characterise patients in a more comprehensive way. Methods: We determined the ASCO score for each patient, according to prospectively collected data using the study protocol. The distribution of aetiologies was analysed with regard to concomitant causes, cryptogenic stroke and different age groups. Results: A potentially causal aetiology (grade 1) was detected in 29.3% of 4,467 patients. Merging grades 1 and 2, a suspected aetiology was found in 54.1%. In 8.6% of patients concomitant aetiologies were identified. Most common causes were cervical arterial dissection and persistent foramen ovale, but there was also a high prevalence of large artery atherosclerosis and SVD especially in older patients of this collective. About 50% of patients had more than one finding with a lower grade of evidence (grade 3). In 14% final classification of strictly cryptogenic stroke was made. Conclusions: This is the largest study to date, using the ASCO characterisation of ischemic stroke aetiologies. ASCO classification provides first evidence that many young patients presenting with acute stroke have concomitant stroke aetiologies associated with a substantial atherosclerosis risk profile. ASCO could be integrated in clinical routine and registry data banks, as well as large clinical trials to improve stroke documentation.

PracticeFor the full versions of these articles see bmj.com a common cause for community acquired pneumonia, but recurrent infections are unusual in a young, healthy non-smoker. Thus repeated infections with these organisms should prompt investigations for possible underlying immunodeficiency.When evaluating patients with recurrent infection, use the acronym SPUR (severe, persistent, unusual, or recurrent) to prompt appropriate investigations for underlying causes. In this case scenario, chronic medical conditions such as diabetes or renal disease, which are associated with an increased tendency to recurrent infection, are effectively excluded by appropriate initial laboratory investigations. The clinical picture does not suggest immunodeficiency involving cellular immunity (most commonly resulting from infection with HIV), although a history of high risk sex or of misuse of intravenous drugs may indicate the need for screening. Secondary antibody deficiencies result most commonly from immunosuppression in lymphoid malignancy or more rarely from protein loss from either the renal or gastrointestinal tracts. Lymphoid malignancies should be considered but are unlikely in the absence of weight loss, fevers, lymphadenopathy, or splenomegaly and with a normal full blood count. The primary antibody deficiency syndromes are a group of rare disorders with a prevalence of around 1 in 50 000 which can present at any age and are characterised by the inability to produce clinically effective antibody responses to infection. With these disorders, delay in diagnosis remains a problem and contributes to chronic disease. He has no weight loss or night sweats. On examination he has bilateral basal crackles in the lungs, normal tympanic membranes, no facial tenderness, and no lymphadenopathy or splenomegaly. A full blood count is normal; random and fasting blood glucose, urea, creatinine, and liver enzymes are all normal, and urinalysis is negative for blood and protein. Sputum culture identifies the presence of Haemophilus influenzae. A chest radiograph is reported as normal.

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