Mechanical detection and pain thresholds: comparability of devices using stepped and ramped stimuli

Quantitative sensory testing is used to assess somatosensory function in humans. The protocol of the German Research Network on Neuropathic Pain (DFNS) provides comprehensive normative values using defined tools; however, some of these may not be feasible in low-resource settings. Objectives: To compare the standard DFNS devices for assessment of mechanosensory function to a low resource tool, the Sorri-Bauru-monofilaments. Methods: Mechanical detection thresholds (MDT), pain thresholds (MPT), and suprathreshold pinprick ratings (pain sensitivity: MPS) were measured over cheek, hand dorsum, and fingertip in 13 healthy subjects (7 female, aged 21-44 years). Mechanical detection threshold was assessed with DFNS standard glass monofilaments (0.25-512 mN, 0.5 mm tip) and nylon monofilaments (Sorri-Bauru; 0.5-3000 mN). MPT was assessed with DFNS standard cylindrical probes (8-512 mN, 0.25 mm tip), Sorri-Bauru monofilaments, and with ramped stimuli using an electronic von Frey aesthesiometer (10 mN/s or 100 mN/s, 0.20 mm tip). MPS was measured in response to stepped and ramped pinpricks (128 and 256 mN). Results: Mechanical detection thresholds were the same for DFNS and Sorri-Bauru monofilaments. For MPT, Sorri-Bauru filaments yielded lower values than PinPricks over face but not hand. Pain thresholds were higher at all test sites for ramped than stepped pinpricks (P < 0.01). Suprathreshold ratings were lower for ramped than stepped pinpricks (P < 0.05). Conclusion: Sorri-Bauru filaments are acceptable substitutes for DFNS standards in estimating tactile sensitivity, but are not consistent with standard probes for pinprick sensitivity because of their nonstandardized tips. Ramped stimuli overestimated MPT and underestimated MPS due to reaction time artefacts and therefore need their own normative values

Magnetospheric Response Times Following Southward IMF Turnings

We analyze the response times of various regions of the magnetosphere-ionosphere system to sudden southward turnings of the IMF. Our data set consists of 26 events during which the IMP BZ component was observed by WIND to change from a stea northward field to a southward field, which subsequently led to a substorm. The magnetospheric response to such IMF southward turnings is examined using data from the POLAR EFI experiment, the GOES 9 magnetometer, and ground magnetometers. The POLAR/EFI was used to investigate changes in the polar cap electric field which occurred in response to the changing interplanetary electric field, and these results are compared with response timings derived from high-latitude ground magnetometers. POLAR/EFI data show responses in the polar cap about 15 minutes after the arrival of the IMF change at the magnetopause. Auroral zone magnetograms and geosynchronous spacecraft measurements are utilized to evaluate the response timing within the closed field line region. In one event examined in detail, the start of a substorm growth phase was observed by GOES 9 in the midnight sector of geosynchronous orbit about two minutes before POLAR observed a response in the polar cap. Using superposed epoch analysis, we calculate typical response times in the polar cap, in the nightside plasma sheet, and in the ionosphere in order to discuss the various suggested mechanisms for information propagation from the subsolar magnetopause into the magnetosphere. We find that for the set of ten events for which the GOES 9 and the CANOPUS array are in the midnight sector, the field at geosynchronous as measured by GOES responds at or before the time of response in the polar cap as measured by POLAR, suggesting different methods of information propagation

Comparing the Clinical and Histological Diagnosis of Leprosy and Leprosy Reactions in the INFIR Cohort of Indian Patients with Multibacillary Leprosy

Leprosy affects skin and peripheral nerves. Although we have antibiotics to treat the mycobacterial infection, the accompanying inflammation is a major part of the disease process. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called reactions. These are associated with worsening of nerve damage. However, diagnosing these reactions is not straightforward. They can be diagnosed clinically by examination or by microscopic examination of the skin biopsies. We studied a cohort of 303 newly diagnosed leprosy patients in India and compared the diagnosis rates by clinical examination and microscopy and found that the microscopic diagnosis has higher rates of diagnosis for both types of reaction. This suggests that clinicians and pathologists have different thresholds for diagnosing reactions. More work is needed to optimise both clinical and pathological diagnosis. In this cohort 43% of patients had Borderline Tuberculoid leprosy, an immunologically active type, and 20% of the biopsies showed only minimal inflammation, perhaps these patients had very early disease or self-healing. The public health implication of this work is that leprosy centres need to be supported by pathologists to help with the clinical management of difficult cases

Comparison of Efficacy and Safety of Ciclosporin to Prednisolone in the Treatment of Erythema Nodosum Leprosum: Two Randomised, Double Blind, Controlled Pilot Studies in Ethiopia.

BACKGROUND: Erythema Nodosum Leprosum (ENL) is a serious complication of leprosy. It is normally treated with high dose steroids, but its recurrent nature leads to prolonged steroid usage and associated side effects. There is little evidence on the efficacy of alternative treatments for ENL, especially for patients who have become steroid resistant or have steroid side effects. These two pilot studies compare the efficacy and side effect profile of ciclosporin plus prednisolone against prednisolone alone in the treatment of patients with either new ENL or chronic and recurrent ENL. METHODS AND RESULTS: Thirteen patients with new ENL and twenty patients with chronic ENL were recruited into two double-blinded randomised controlled trials. Patients were randomised to receive ciclosporin and prednisolone or prednisolone treatment only. Patients with acute ENL had a delay of 16 weeks in the occurrence of ENL flare-up episode, with less severe flare-ups and decreased requirements for additional prednisolone. Patients with chronic ENL on ciclosporin had the first episode of ENL flare-up 4 weeks earlier than those on prednisolone, as well as more severe ENL flare-ups requiring 2.5 times more additional prednisolone. Adverse events attributable to prednisolone were more common that those attributable to ciclosporin. CONCLUSIONS: This is the first clinical trial on ENL management set in the African context, and also the first trial in leprosy to use patients' assessment of outcomes. Patients on ciclosporin showed promising results in the management of acute ENL in this small pilot study. But ciclosporin, did not appear to have a significant steroid-sparing effects in patients with chronic ENL, which may have been due to the prolonged use of steroids in these patients in combination with a too rapid decrease of steroids in patients given ciclosporin. Further research is needed to determine whether the promising results of ciclosporin in acute ENL can be reproduced on a larger scale

Leprosy in a patient infected with HIV

A 60-year-old Nigerian man, who had lived in Europe for 30 years but had returned home frequently, presented with right frontalis muscle weakness and right ulnar nerve palsy, without skin lesions. Neurophysiology showed a generalised neuropathy with demyelinating features. Blood tests were positive for HIV, with a normal CD4 count. There was nerve thickening both clinically and on MRI. Nerve biopsy showed chronic endoneuritis and perineuritis (indicating leprosy) without visible mycobacteria. His neuropathy continued to deteriorate (lepra reaction) before starting treatment with WHO multidrug therapy, highly active antiretroviral therapy and corticosteroids. There are 10 new cases of leprosy diagnosed annually in the UK. Coinfection with HIV is rare but paradoxically does not usually adversely affect the outcome of leprosy or change treatment. However, permanent nerve damage in leprosy is common despite optimal therapy. Leprosy should be considered in patients from endemic areas who present with mononeuritis multiplex

Cytokine and Protein Markers of Leprosy Reactions in Skin and Nerves: Baseline Results for the North Indian INFIR Cohort

Leprosy affects skin and peripheral nerves. Although we have effective antibiotics to treat the mycobacterial infection, a key part of the disease process is the accompanying inflammation. This can worsen after starting antibacterial treatment with episodes of immune mediated inflammation, so called ‘reactions’. These reactions are associated with worsening of the nerve damage. We recruited a cohort of 303 newly diagnosed leprosy patients in North India with the aim of understanding and defining the pathological processes better. We took skin and nerve biopsies from patients and examined them to define which molecules and mediators of inflammation were present. We found high levels of the cytokines Tumour Necrosis Factor alpha, Transforming Growth Factor beta and inducible Nitric Oxide Synthase in biopsies from patients with reactions. We also found high levels of bacteria and inflammation in the nerves. These experiments tell us that we need to determine which other molecules are present and to explore ways of switching off the production of these pro-inflammatory molecules

Analysis of Antibody and Cytokine Markers for Leprosy Nerve Damage and Reactions in the INFIR Cohort in India

Leprosy is one of the oldest known diseases. In spite of the established fact that it is least infectious and a completely curable disease, the social stigma associated with it still lingers in many countries and remains a major obstacle to self reporting and early treatment. The nerve damage that occurs in leprosy is the most serious aspect of this disease as nerve damage leads to progressive impairment and disability. It is important to identify markers of nerve damage so that preventive measures can be taken. This prospective cohort study was designed to look at the potential association of some serological markers with reactions and nerve function impairment. Three hundred and three newly diagnosed patients from north India were recruited for this study. The study attempts to reflect a model of nerve damage initiated by mycobacterial antigens and maintained by ongoing inflammation through cytokines such as Tumour Necrosis Factor alpha and perhaps extended by antibodies against nerve components