An International Perspective on Preceding Infections in Guillain-Barré Syndrome: The IGOS-1000 Cohort.

BACKGROUND AND OBJECTIVES: Infections play a key role in the development of Guillain-Barré syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale. METHODS: We analyzed the first 1,000 patients included in the International GBS Outcome Study with available biosamples (n = 768) for the presence of a recent infection with Campylobacter jejuni, hepatitis E virus, Mycoplasma pneumoniae, cytomegalovirus, and Epstein-Barr virus. RESULTS: Serologic evidence of a recent infection with C. jejuni was found in 228 (30%), M. pneumoniae in 77 (10%), hepatitis E virus in 23 (3%), cytomegalovirus in 30 (4%), and Epstein-Barr virus in 7 (1%) patients. Evidence of more than 1 recent infection was found in 49 (6%) of these patients. Symptoms of antecedent infections were reported in 556 patients (72%), and this proportion did not significantly differ between those testing positive or negative for a recent infection. The proportions of infections were similar across continents. The sensorimotor variant and the demyelinating electrophysiologic subtype were most frequent across all infection groups, although proportions were significantly higher in patients with a cytomegalovirus and significantly lower in those with a C. jejuni infection. C. jejuni-positive patients were more severely affected, indicated by a lower Medical Research Council sum score at nadir (p = 0.004) and a longer time to regain the ability to walk independently (p = 0.005). The pure motor variant and axonal electrophysiologic subtype were more frequent in Asian compared with American or European C. jejuni-positive patients (p < 0.001, resp. p = 0.001). Time to nadir was longer in the cytomegalovirus-positive patients (p = 0.004). DISCUSSION: Across geographical regions, the distribution of infections was similar, but the association between infection and clinical phenotype differed. A mismatch between symptom reporting and serologic results and the high frequency of coinfections demonstrate the importance of broad serologic testing in identifying the most likely infectious trigger. The association between infections and outcome indicates their value for future prognostic models.

Manifestations of HIV infection in the peripheral nervous system.

Peripheral nerve disorders are associated with all stages of HIV infection. Distal sensory polyneuropathy is characterised by often-disabling pain that is difficult to treat. It is prevalent in both high-income and low-income settings. In low-income settings, use of potentially neurotoxic antiretrovirals, which are inexpensive and widely available, contributes substantially to incidence. Research has focused on identification of factors that predict risk of distal sensory polyneuropathy and elucidation of the multifactorial mechanisms behind pathogenesis. Sensorimotor polyneuropathies and polyradiculopathies are less frequent than distal sensory polyneuropathy, but still occur in low-income settings and have potentially devastating consequences. However, many of these diseases can be treated successfully with a combination of antiretroviral and immune-modulating therapies. To distinguish between peripheral nerve disorders that have diverse, overlapping, and frequently atypical presentations can be challenging; a framework based on a clinicoanatomical approach might assist in the diagnosis and management of such disorders.

Reliability and diagnostic performance of CT imaging criteria in the diagnosis of tuberculous meningitis.

INTRODUCTION: Abnormalities on CT imaging may contribute to the diagnosis of tuberculous meningitis (TBM). Recently, an expert consensus case definition (CCD) and set of imaging criteria for diagnosing basal meningeal enhancement (BME) have been proposed. This study aimed to evaluate the sensitivity, specificity and reliability of these in a prospective cohort of adult meningitis patients. METHODS: Initial diagnoses were based on the CCD, classifying patients into: 'Definite TBM' (microbiological confirmation), 'Probable TBM' (diagnostic score ≥10), 'Possible TBM' (diagnostic score 6-9), 'Not TBM' (confirmation of an alternative diagnosis) or 'Uncertain' (diagnostic score of <6). CT images were evaluated independently on two occasions by four experienced reviewers. Intra-rater and inter-rater agreement were calculated using the kappa statistic. Sensitivities and specificities were calculated using both 'Definite TBM' and either 'Definite TBM' or 'Probable TBM' as gold standards. RESULTS: CT scan criteria for BME had good intra-rater agreement (κ range 0.35-0.78) and fair to moderate inter-rater agreement (κ range 0.20-0.52). Intra- and inter-rater agreement on the CCD components were good to fair (κ  =  ranges 0.47-0.81 and 0.21-0.63). Using 'Definite TBM' as a gold standard, the criteria for BME were very specific (61.5%-100%), but insensitive (5.9%-29.4%). Similarly, the imaging components of the CCD were highly specific (69.2-100%) but lacked sensitivity (0-56.7%). Similar values were found when using 'Definite TBM' or 'Probable TBM' as a gold standard. DISCUSSION: The fair to moderate inter-rater agreement and poor sensitivities of the criteria for BME suggest that little reliance should be placed in these features in isolation. While the presence of the CCD criteria of acute infarction or tuberculoma(s) appears useful as rule-in criteria, their absence is of little help in excluding TBM. The CCD and criteria for BME, as well as any new criteria, need to be standardized and validated in prospective cohort studies.