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

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/

The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in North India

The aim of this study was to find predictors of neuropathy and reactions, determine the most sensitive methods for detecting peripheral neuropathy, study the pathogenesis of neuropathy and reactions and create a bank of specimen, backed up by detailed clinical documentation. A multi-centre cohort study of 303 multibacillary leprosy patients in Northern India was followed for 2 years. All newly registered MB patients requiring a full course of MDT, who were smear positive and/or had six or more skin lesions and/or had two or more nerve trunks involved, were eligible. A detailed history was taken and physical and neurological examinations were performed. Nerve function was assessed at each visit with nerve conduction testing, warm and cold detection thresholds, vibrometry, dynamometry, monofilaments and voluntary muscle testing. Because the latter two are widely used in leprosy clinics, they were used as ‘gold standard’ for sensory and motor impairment. Other outcome events were type 1 and 2 reactions and neuritis. All subjects had a skin biopsy at registration, repeated at the time of an outcome event, along with a skin biopsy at registration, repeated at the time of an outcome event, along with a nerve biopsy. These were examined using a variety immunohistological techniques. Blood sampling for serological testing was done at every 4-weekly clinic visit. At diagnosis, 115 patients had an outcome event of recent onset. Many people had skin lesions overlying a major nerve trunk, which were shown to be significantly associated with an increased of sensory or motor impairment. The most important adjusted odds ratios for motor impairment were, facial 4.5 (1.3-16) and ulnar 3.5 (1.0-8.5); for sensory impairment they were, ulnar 2.9 (1.3-6.5), median 3.6 (1.1-12) and posterior tibial 4.0 (1.8-8.7). Nerve enlargement was found in 94% of patients, while only 24% and 3% had paraesthesia and nerve tenderness on palpation, respectively. These increased the risk of reactions only marginally. Seven subjects had abnormal tendon reflexes and seven abnormal joint position sense. In all but one case, there impairments were accompanied by abnormalities in two or more other nerve function tests and thus seemed in indicate more serve neuropathy. At diagnosis, 38% of a cohort of newly diagnosed MB leprosy patients had recent or new reactions or nerve damage at the time of intake into the study. The main risk factor for neuropathy found in this baseline analysis was the presence of skin lesions overlying nerve trunks. They increased the risk of sensory or motor impairment in the concerned nerve by 3-4 times. For some nerves, reactional signs in the lesions further increased this risk to 6-8 times the risk for those without such lesions. Patients with skin lesions overlying peripheral nerve trunks should be carefully monitored for development of sensory or motor impairment

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

Neurology Asia15139-5

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

Neurology Asia142129-13