Antónia Turkman

Motor responses evoked by transcranial magnetic stimulation and peripheral nerve stimulation in the ulnar innervation in amyotrophic lateral sclerosis: the effect of upper and lower motor neuron lesion

We studied the upper (UMN) and lower motor neuron (LMN) innervations of 159 hands from 81 patients with amyotrophic lateral sclerosis (ALS). Eleven patients with various chronic LMN disorders causing weakness in the abductor digiti minimi (ADM) muscle served as LMN controls. Thirty healthy subjects served as normal controls. Cortical motor threshold, central conduction time (CMCT), and motor-evoked response amplitude (MEP) after transcranial magnetic stimulation (TMS) were studied, and the MEP/M wave ratio was calculated. The data was analyzed in the ALS subjects in groups defined by ADM muscle strength and by the presence or absence of clinical signs of UMN involvement. CMCT was not increased in the ALS or LMN disease groups. The threshold was higher in limbs with both weak ADM muscles and UMN signs. The MEP/M wave amplitude ratio was increased in weak muscles in the ALS patients, notably in limbs with no UMN signs, and also in weak muscles in patients with other chronic LMN disorders. It was frequently decreased in strong muscles. There was no difference between bulbar-onset and limb-onset ALS groups, and there was no correlation between threshold and disease duration. We suggest that expressing the data as an index and utilising the MEP/M wave amplitude ratio as a variable is a sensitive method for detecting UMN abnormality in ALS in particular in early affected muscles.

Motor unit firing in amyotrophic lateral sclerosis and other upper and lower motor neurone disorders

OBJECTIVE Motor unit recruitment order and firing rate was investigated in healthy subjects, and in small numbers of patients 50years ago. We aimed to investigate firing rate in different disorders, testing the same target muscle with normal strength, to evaluate possible application in diagnosing upper motor neuron (UMN) lesion. METHODS We studied motor unit firing in the tibialis anterior muscle in six groups of subjects; normal subjects (n=45), patients with amyotrophic lateral sclerosis (ALS) (n=36), primary lateral sclerosis (PLS) (n=21), progressive muscular atrophy (PMA) (n=14), various upper motor neurone lesions (n=16) and polyneuropathy (n=42). In all these subjects the tibialis anterior muscle was of normal strength. Motor units were recruited during slight contraction in order to study 2-5 motor units at each recording site, using a standard concentric needle electrode, so that 20-22 motor units were recorded in each muscle. We analysed the coefficient of variation (CV) for amplitude, area, duration and firing rate in these motor units, and the correlation between motor unit potential size and recruitment order. RESULTS The mean MU firing rate in this task was similar in each group. No recruitment order was disclosed within the limits of the study task. The CV of firing rate was decreased in UMN and PLS groups. ALS patients with marked spasticity showed a lower CV of motor unit firing rate. The CV of amplitude, area and duration was similar between groups. CONCLUSIONS These results in tibialis anterior indicate that physiological modulation of lower motor neuron (LMN) firing rate is decreased in patients with lower limb spasticity. The variability of MU discharges tends to be greater in diseases affecting the LMN. SIGNIFICANCE These results suggest that, notwithstanding the simplicity of the task we have used, the physiological variability of motor unit firing may be a useful variable in assessing UMN involvement in motor system disorders.

Sensitivity of MUP parameters in detecting change in early ALS

OBJECTIVES We aimed to identify the most appropriate MUP parameter to evaluate reinnervation in very early ALS. METHODS We studied tibialis anterior (TA), initially of normal strength with normal MUP analysis parameters, in 15 patients with ALS of recent onset. They were studied at the initial diagnostic assessment, and then 3 and 6 months later. Spontaneous EMG activity was recorded. Conventional MUP analysis included mean amplitude, mean area, mean duration, mean number of phases, mean number of turns, % polyphasic potentials, mean jitter, % unstable pairs and % pairs with blocking. Non-parametric statistics were utilised in the analysis. RESULTS Fasciculations were recorded in 72% in TA and increased jitter in 33% at study entry, but without EMG features of denervation. Mean amplitude, mean duration, mean area and the three measures of neuromuscular transmission increased significantly and linearly at each evaluation. Median duration showed the lowest variation and, together with jitter, the largest relative time effect. CONCLUSIONS Mean duration and mean jitter are the most effective measures of early reinnervation in a very early affected muscle, in ALS. SIGNIFICANCE Mean MUP duration is a simple and easy measure that should be useful in evaluating reinnervation, for example in a future clinical trial.

Religious Affiliation Modulates Weekly Cycles of Cropland Burning in Sub-Saharan Africa

Vegetation burning is a common land management practice in Africa, where fire is used for hunting, livestock husbandry, pest control, food gathering, cropland fertilization, and wildfire prevention. Given such strong anthropogenic control of fire, we tested the hypotheses that fire activity displays weekly cycles, and that the week day with the fewest fires depends on regionally predominant religious affiliation. We also analyzed the effect of land use (anthrome) on weekly fire cycle significance. Fire density (fire counts.km-2) observed per week day in each region was modeled using a negative binomial regression model, with fire counts as response variable, region area as offset and a structured random effect to account for spatial dependence. Anthrome (settled, cropland, natural, rangeland), religion (Christian, Muslim, mixed) week day, and their 2-way and 3-way interactions were used as independent variables. Models were also built separately for each anthrome, relating regional fire density with week day and religious affiliation. Analysis revealed a significant interaction between religion and week day, i.e. regions with different religious affiliation (Christian, Muslim) display distinct weekly cycles of burning. However, the religion vs. week day interaction only is significant for croplands, i.e. fire activity in African croplands is significantly lower on Sunday in Christian regions and on Friday in Muslim regions. Magnitude of fire activity does not differ significantly among week days in rangelands and in natural areas, where fire use is under less strict control than in croplands. These findings can contribute towards improved specification of ignition patterns in regional/global vegetation fire models, and may lead to more accurate meteorological and chemical weather forecasting.

Modulation of fasciculation frequency in amyotrophic lateral sclerosis

Fasciculations are a major clinical feature, present very early in the natural history of amyotrophic lateral sclerosis (ALS).1 They represent spontaneous discharges of motor units or portions of motor units, that can sometimes also be activated volitionally.2 There is no objective evidence that fasciculation potential (FP) discharges can be modulated by the patient or by the examiner. In this study we have addressed this issue in ALS, spinal muscular atrophy (SMA) and benign fasciculation syndrome (BFS). We evaluated fasciculation firing frequency, using surface electromyographic (EMG) recordings from the first dorsal interosseous (DI) muscle in the hand at rest, and randomly after a period of maximal contraction, thus involving upper and lower motor neuron excitation, after radial sensory nerve stimulation and after supramaximal electrical stimulation of the ulnar nerve at the wrist, representing lower motor neuron excitation. We studied 75 patients with definite or probable ALS, excluding patients with polyneuropathy, diabetes or ulnar neuropathy (median age 61 years (range 27–75 years), median disease duration 12 months (range 3–24 months), 48 were men). One hand, in which first DI strength was 4 on the MRC (Medical Research Council) score 4 or 5, was studied in each patient. In each participant, FPs were recorded at rest in the first DI muscle. Six patients with SMA type 3 were studied (median age 45 years; range 28–60 years). …

Healthcare recommendations from the Personalised ICT Supported Service for Independent Living and Active Ageing (PERSSILAA) Study

In the face of demographic ageing European healthcare providers and policy makers are recognising an increasing prevalence of frail, community-dwelling older adults, prone to adverse healthcare outcomes. Prefrailty, before onset of functional decline, is suggested to be reversible but interventions targeting this risk syndrome are limited. No consensus on the definition, diagnosis or management of pre-frailty exists. The PERsonalised ICT Supported Service for Independent Living and Active Ageing (PERSSILAA) project (2013-2016 under Framework Programme 7, grant #610359) developed a comprehensive Information and Communication Technologies (ICT) supported platform to screen, assess, manage and monitor pre-frail community-dwelling older adults in order to address pre-frailty and promote active and healthy ageing. PERSSILAA, a multi-domain ICT service, targets three pre-frailty: nutrition, cognition and physical function. The project produced 42 recommendations across clinical (screening, monitoring and managing of pre-frail older adults) technical (ICT-based innovations) and societal (health literacy in older adults, guidance to healthcare professional, patients, caregivers and policy makers) areas. This paper describes the 25 healthcare related recommendations of PERSSILAA, exploring how they could be used in the development of future European guidelines on the screening and prevention of frailty.

Bayesian classification for bivariate normal gene expression

A Bayesian optimal screening method (BOSc) is proposed to classify an individual into one of two groups, based on the observation of pairs of covariates, namely the expression level of pairs of genes (previously selected by a specific method, among the thousands of genes present in the microarray) measured using DNA microarrays technology. The method is general and can be applied to any correlated pair of screening variables, either with a bivariate normal distribution or which can be transformed into a bivariate normal. Results on microarray data sets (Leukemia, Prostate and Breast) show that BOSc performance is competitive with, and in some cases significantly better than, quadratic and linear discriminant analyses and support vector machines classifiers. BOSc provides flexible parametric decision rules. Finally, the screening classifier allows the calculation of operating characteristics while addressing information about the prevalence of the disease or type of disease, which is an advantage over other classification methods.

ICT-Supported Interventions Targeting Pre-frailty: Healthcare Recommendations from the Personalised ICT Supported Service for Independent Living and Active Ageing (PERSSILAA) Study

As society ages, healthcare systems are preparing for an increasing prevalence of frail, co-morbid and older community-dwellers at risk of adverse outcomes including falls, malnutrition, hospitalisation, institutionalisation and death. Early intervention is desirable and pre-frailty, before onset of functional decline, may represent a suitable transition stage to target, albeit evidence for reversibility and appropriate interventions are limited. No consensus on the definition, diagnosis or management of pre-frailty exists. This work describes 25 healthcare related findings from the recently completed PERsonalised ICT Supported Service for Independent Living and Active Ageing (PERSSILAA) project, funded under the 2013–2016 European Union Framework Programme 7 (grant #610359). PERSSILAA developed a comprehensive Information and Communication Technologies (ICT)-supported platform to screen, assess, intervene and then monitor community-dwellers in two regions (Enschede in the Netherlands and Campania in Italy) in order to address pre-frailty and promote active and healthy ageing, targeting three important pre-frailty subdomains: nutrition, cognition and physical function. Proposed definitions of pre-frailty, ICT-based approaches to screen and monitor for the onset of frailty and targeted management strategies employing technology across these domains are described. The potential of these 25 healthcare recommendations in the development of future European guidelines on the screening and prevention of frailty is explored.