Reference values for nerve function assessments among a study population in northern India - III: sensory and motor nerve conduction

Objective: To identify reference values for normal sensory and motor nerve conduction in upper andlower limb peripheral nerves in a study population in India. The work was carried out in advanceof the INFIR Cohort Study, a prospective study of individuals with newly diagnosed multibacillaryMB leprosy, the objective being to identify early changes in nerve function predictive of new onsetimpairment and reactions. Methods: We assessed sensory nerve conduction in bilateral ulnar, median,radial cutaneous and sural nerves and motor nerve conduction in distal and proximal sites in bilateralulnar, median and peroneal nerves among 315 healthy subjects. After adjustment for skin temperatureand removal of outliers reference values were computed using regression analysis of log-transformeddata. The analysis and resulting reference values were stratifi ed by age and sex and based on theappropriate 5th or 95th percentiles. Results: Presented here are reference values for sensory nerveconduction velocity (SNCV), sensory nerve action potential (SNAP) amplitude and latency. Also formotor nerve conduction velocity (MNCV) and compound motor action potential (CMAP) amplitudeat proximal sites and for amplitude and latency at distal sites. In each case percentiles are given bysex within four 10 year age bands. For males aged 55 years old, the reference value for ulnar SNCVwas 43.6 m/sec and SNAP amplitude was 7.43 ?V. Ulnar MNCV at the proximal site in the elbowwas 50.8 m/sec and CMAP amplitude 7.25 mV and at distal sites in the wrist the amplitude was 7.14mV and latency 3.1 msec. In the leprosy-affected cohort, the most common and therefore potentiallythe earliest impairment, is found in sensory nerve conduction amplitude of the sural nerve

Reference values for nerve function assessments among a study population in northern India - I. Vibration perception thresholds

Objective: this paper presents normal reference values for vibration perception thresholds for a study population in northern India. The work was in preparation for the INFIR Cohort Study, a prospective study of people newly diagnosed with multibacillary leprosy which sought to identify early changes in nerve function predictive of new onset impairment and reactions. To establish the limits of normalfunction we collected data on subjects with no known neurological condition and computed the referencevalues defining the limits of normal function.Methods: data on vibration perception in 5 bilateral nerves was collected from 362 healthy subjects stratified by sex and by age and drawn from the same general population as the subsequent leprosy-affected cohort. Reference values were computed from log-transformed data after the exclusion of outliers. Results: normal reference values are presented in the form of 95th percentiles for vibration perception thresholds among normal subjects for 5 peripheral nerves within 8 age and sex groupings and by centre. The reference values are compared with those published for other populations. The incidence of impairment at diagnosis among the leprosy-affected cohort is described and illustrate

Clinical outcomes in a randomized controlled study comparing azathioprine and prednisolone versus prednisolone alone in the treatment of severe leprosy type 1 reactions in Nepal

The ILEP nerve function impairment and reaction research programme (INFIR 2) was a group of clinical trials conducted to identify second-line treatments for severe leprosy type 1 reactions (T1R). This paper presents the clinical results of one of these trials in which azathioprine was used in combination with short-course prednisolone to ascertain if the combination was effective in controlling the symptoms and signs of reaction. Forty patients were alternately assigned to a 12-week treatment with either AP (12 weeks azathioprine at 3 mg/kg/d plus 8 week reducing course prednisolone starting at 40 mg/d) or P (12-week reducing course prednisolone starting at 40 mg/d). Evaluation included serial quantitative clinical assessments. The overall frequency of side effects was similar in both groups. Results show that there was no difference in clinical outcome in the AP and P groups and a similar number of patients in each group required extra prednisolone for worsening clinical features. We conclude that a 12-week course of azathioprine at 3 mg/kg/day plus an 8 week reducing course of prednisolone starting at 40 mg/d is as effective as a 12 week reducing course of prednisolone starting at 40 mg/d and that the combination therapy is well-tolerated in severe leprosy T1R patients

The INFIR Cohort Study: assessment of sensory and motor neuropathy in leprosy at baseline

Aim: To compare different method(s) to detect peripheral neuropathy in leprosy and to study the validity of the monofilament test (MF) and the voluntary muscle test (VMT) as standard tests of nerve function.Design: A multi-centre cohort study of 303 multibacillary (MB) leprosy patients.Methods: Newly registered MB patients requiring a full course of MDT were recruited in two leprosy outpatient clinics in North India. Controls were people without leprosy or neurological conditions, attending the dermatological outpatient departments of the same clinics. Nerve function was evaluated electrophysiologically using standard parameters for sensory and motor nerve conduction (NC) testing, warm and cold detection thresholds (W/CDT), vibration perception thresholds, dynamometry, MF and VMT. The latter two defined the outcomes of sensory and motor impairment.Results: 115 patients had nerve damage or a reaction of recent onset at diagnosis. Sensory and motor amplitudes and WDTs were the most frequently abnormal. Among the nerves tested, the sural and posterior tibial were the most frequently impaired. In the ulnar nerve, sensory latencies were abnormal in 25% of subjects; amplitudes in 40%. Ulnar above-elbow motor conduction velocities were abnormal in 39% and amplitudes 32%. WDTs were much more frequently affected than CDTs in all nerves tested. The thresholds of all test parameters differed significantly between controls and patients, while only some differed between patients with and without reaction. Good concordance was observed between MF results and sensory latencies and velocities (direct concordance 80%for the ulnar). However, a proportion of nerves with abnormal MF results tested normal on one or more of the other tests or vice versa. Concordance between VMT and motor conduction velocities was good for the ulnar nerve, but for the median and peroneal nerves, the proportion impaired by VMT out of those with abnormal motor conduction was very low. Conclusions: Concordance between monofilaments and other sensory function test results was good, supporting the validity of the monofilaments as standard screening test of sensory function. Concordance between VMT results and motor nerve conduction was good for the ulnar nerve, but very few median and peroneal nerves with abnormal conduction had an abnormal VMT. A more sensitive manual motor test may be needed for these nerves. Of the nerve assessment tests conducted, NC amplitudes and warm sensation were the most frequently affected. Therefore, nerve conduction studies and WDT measurements appear to be most promising tests for early detection of leprous neuropathy. The pattern of concordance between tactile and thermal sensory impairment failed to support the hypothesis that small fibre neuropathy always precedes large fibre damage. Warm sensation was more frequently affected than cold sensation. This could indicate that unmyelinated C fibres are more frequently affected than small myelinated Ad fibres

Reference values for nerve function assessments among a study population in northern India - II: thermal sensation thresholds

Objective: This paper presents normal reference values for thermal sensation for a study populationwith no known neurological condition in northern India. It was part of the INFIR Cohort Study, aprospective study of people newly diagnosed with multibacillary leprosy, the objective being to identifyearly changes in nerve function predictive of new onset impairment and reactions. Methods: Data onwarm and cold sensation in fi ve bilateral nerves was collected from 326 healthy subjects stratifi ed bysex and by age and drawn from the same general population as the subsequent leprosy-affected cohort.Reference values were computed from log-transformed data after the exclusion of outliers. Results:Normal reference values are presented in the form of 95th percentiles for warm and 5th percentilefor cold sensation within eight age and sex groups and by centre. The prevalence of impairment atdiagnosis among the leprosy-affected cohort is described and illustrated The high prevalence of lostwarm sensation in the leprosy-affected cohort suggests that this is an important early indicator fornerve involvement in leprosy

The histological diagnosis of leprosy type 1 reactions: identification of key variables and an analysis of the process of histological diagnosis

Background: Type 1 leprosy reactions (T1R) are a major inflammatory complication of leprosy affecting 30% of patients with borderline leprosy, but there has been no diagnostic evaluation of the histological diagnosis of this entity. Methods: In a prospective study based in India, skin biopsies were taken from 99 patients with clinically diagnosed T1R and 52 non-reactional controls. These were assessed histologically by four histopathologists whose assessments were then compared. Results: Reactions were under-diagnosed, with 32–62% of clinically diagnosed reactions being given a histological diagnosis. The pathologists showed good specificities (range 72% to 93%) but much poorer sensitivities (range 42% to 78%). The most commonly reported histological features of TIR were cell maturity, oedema and giant cells. Five key variables were identified that the pathologists used in diagnosing a reaction: intra-granuloma oedema, giant cell size, giant cell numbers, dermal oedema and HLA-DR expression. A predictive model for the diagnosis of T1R was developed using stepwise logistic regression analysis, with clinical diagnosis of reaction as an outcome, and then identification of the key variables that each pathologist used in making the diagnosis of T1R. 34–53% of the variation between pathologists could be accounted for. The four pathologists used a similar diagnostic model and for all of them their estimations of epithelioid cell granuloma oedema, dermal oedema, plasma cells and granuloma fraction were significant variables in the diagnosis of T1R. Each pathologist then added in variables that were specific to themselves. Conclusions: This study has identified T1R as being under-diagnosed in comparison with clinical assessments. Key variables for diagnosing T1R were established. This comparative masked study highlights the need for such studies in other inflammatory conditions. <br/

Reference values for nerve function assessments among a study population in northern India - iii: Sensory and motor nerve conduction

Neurology Asia15139-5