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Biomedical subjects

P G Bain

Publications and source records attributed to P G Bain.

At least 19 recordsLinked to original sources

Evaluation of three different ways of assessing tremor in multiple sclerosis.

OBJECTIVES: To examine the comparative reliability and validity of three simple ways of rating upper limb tremor in patients with multiple sclerosis. METHODS: Three examiners independently rated severity of upper limb tremor in patients with multiple sclerosis on a 0-10 scale by studying videotape recordings of patients' examinations, spiral drawings, and handwriting samples. The correlations of the tremor severity scores with scores from arm dexterity tests and a tremor related disability scale were also assessed. RESULTS: Rating tremor on posture had a good intrarater and interrater reliability. However, these reliabilities decreased when kinetic tremor was assessed, in part because dysmetria was a confounding factor. The intrarater reliabilities of rating tremor from spirals and handwriting were also good but the interrater reliabilities were only fair to moderate. Tremor severity scored by all three methods correlated highly with scores obtained from the nine hole peg test, finger tapping test, and a tremor related activities of daily living (ADL) questionnaire, indicating that all three methods were valid ways of assessing tremor in multiple sclerosis. CONCLUSION: Multiple sclerosis tremors in posture can be scored using a clinical rating scale in a valid and reliable way, and from spirals and handwriting samples if the ratings are carried out by the same examiner. However, scoring kinetic tremor was less reliable. In addition, the nine hole peg and finger tapping tests provide useful objective assessments of upper limb function in tremulous patients with multiple sclerosis.

Activities of Daily Living↗

Tremor assessment and quality of life measurements.

Essential tremor (ET) can be measured objectively by physiological techniques, simple tests of the tremor's impact on function, or subjective use of clinical rating scales. The methods of measuring ET and its influence on patients are reviewed. Multidimensional evaluations are recommended for the assessment of the severity of ET in clinical trials. The term "detractor" describes the relationships between ET and the disability and handicap that it produces.

Diagnosis, Differential↗

Classification of normal and pathological tremors using a multidimensional electromagnetic system.

A new multidimensional movement analysis system was used to record limb tremor over six degrees-of-freedom, and signal processing techniques were explored to develop a suitable classification method to distinguish between different types of tremor. The specific aims were to investigate the ability of the system to screen for differences between normal subjects and a group of neurological patients, and then to differentiate between three diagnostic groups of patients. Postural tremor at the hand was recorded in normal subjects (n=24) and patients with essential tremor (n=21), multiple sclerosis (n=17) and parkinsonism (n=19). Data were collected using a 3Space Fastrak((R)) (Polhemus, Inc.) over six degrees-of-freedom (three translational directions and three rotations). Spectral estimates produced measures of tremor frequency and amplitude. Mathematical models of the data, using autoregressive modelling and K-nearest neighbour classification, produced parameters used to classify, (1) the normal subjects and 24 patients (using the three rotational movements), and (2) the three patient groups (using all six movement directions). Results were given in terms of the probability of each subject belonging to the groups being classified. 70%). The diagnostic classification produced clear differences between the patient groups (60% for essential tremor, 80% for multiple sclerosis and 60% for parkinsonism). The ability of this assessment technique to distinguish between postural tremor in normal subjects and neurological patients suggests that it could be developed as a screening tool. Classification of tremors between the patients groups, with a high degree of sensitivity, indicates the potential for further development of the system as a diagnostic aid.

Adult↗

A comparison of fast Fourier transform (FFT) and autoregressive (AR) spectral estimation techniques for the analysis of tremor data.

This review outlines the theory of spectral estimation techniques based on the fast Fourier transform (FFT) and autoregressive (AR) model and their application to the analysis of human tremor data. Two FFT-based spectral estimation techniques are presented, the Blackman-Tukey and periodogram methods. Factors that influence the quality of spectral estimates are discussed including the choice of windowing function. The theory of parametric modelling is introduced and AR modelling identified as the technique best suited to the analysis of tremor data. The processes of parameter estimation and model order selection are described. The theory of AR spectral estimation is outlined and differences between the AR and FFT-based spectral estimates are summarised. A brief guide to the implementation of FFT-based and AR spectral estimation techniques is given concentrating on data analysis packages that require little or no programming expertise. This review concludes that the AR modelling approach can produce tremor spectra that are superior to those from FFT-based methods for short data sequences. Although the spectral estimates are improved, the benefits of AR modelling for providing information about the physiological mechanisms of tremor generation are not yet clear.

Algorithms↗

Clinical measurement of tremor.

Multidimensional evaluations are recommended for the assessment of tremor severity in clinical trials. The precise method of measuring a particular tremor influences the results of the measurement. Furthermore, complex natural tremor amplitude perturbations introduce the potential for sampling errors.

Disability Evaluation↗

Tremor associated with benign IgM paraproteinaemic neuropathy.

The clinical and neurophysiological features of six patients with action tremor of the upper limbs associated with IgM paraproteinaemic neuropathy are described. Symptomatic tremor was confined to the upper limbs and was broadly symmetrical. The frequency of associated rhythmic muscle activity ranged from 2.8 to 5.5 Hz in abductor pollicis brevis and from 3.7 to 5.5 Hz in the forearm flexor muscles. Magnetic brain stimulation, somatosensory evoked potentials (SEPs) and stretch reflex studies did not provide evidence for delayed conduction within central pathways. There was marked slowing of the maximum motor conduction velocities in peripheral nerves. Forearm stretch reflexes were present but their latencies were prolonged. Somatosensory evoked potentials were obtained in the majority of patients, but were delayed. Wrist tremor could be modulated by mechanical perturbations or median nerve electrical shocks. Simple voluntary wrist movements were of normal duration and peak velocity, but the kinematic profile was asymmetric. Each movement was associated with a triphasic EMG pattern in agonist-antagonist-agonist muscles but the durations of the bursts were prolonged and the onset of the second agonist was delayed. These results support the hypothesis that distorted, mistimed peripheral inputs reach a central processor (probably the cerebellum) which although intact is misled into producing tremor in certain parts of the body.

Aged↗

Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome.

Intravenous immunoglobulin improves many antibody-mediated autoimmune disorders, but its mode of action is unknown. We investigated its effects on muscle strength and on the serum titer of the calcium-channel autoantibodies that are likely to be pathogenic in the Lambert-Eaton myasthenic syndrome (LEMS). In a randomized, double-blind, placebo-controlled crossover trial, serial indices of limb, respiratory, and bulbar muscle strength and the serum titer of calcium-channel antibodies in nine patients were compared over an 8-week period, using the area-under-the-curve approach, following infusion on two consecutive days of immunoglobulin at 1 g/kg body weight/day (total dose 2.0 g/kg body weight) or placebo (equivalent volume of 0.3% albumin). Calcium-channel antibodies were measured by radioimmunoassay using 125I-omega-conotoxin MVIIC. Direct anti-idiotypic actions of immunoglobulin were tested in this assay. Immunoglobulin infusion was followed by significant improvements in the three strength measures (p = 0.017 to 0.038) associated with a significant decline in serum calcium-channel antibody titers (p = 0.028). Improvement peaked at 2 to 4 weeks and was declining by 8 weeks. Mean serum titers were unchanged at 1 week, however, and direct anti-idiotypic neutralization by immunoglobulin was not demonstrable in vitro. We conclude that immunoglobulin causes a short-term improvement in muscle strength in LEMS that probably results from the induced reduction in calcium-channel autoantibodies. The reduction is not due to a direct neutralizing action of the immunoglobulin, but a delayed anti-idiotypic action cannot be excluded. Improvement following intravenous immunoglobulin in other autoantibody-mediated disorders may similarly be associated with decline in levels of pathogenic autoantibodies.

Adolescent↗

Primary writing tremor.

Primary writing tremor (PWT) is considered to be a type of task-specific tremor in which tremor predominantly occurs and interferes with handwriting. We describe the clinical and neurophysiological features of 21 patients (20 male and one female) with PWT. Mean age at tremor onset was 50.1 years. A family history of PWT was obtained from seven patients. Ten patients obtained benefit from drug treatment (mainly propranalol or primidone) and seven responded to alcohol. The writing speeds of the patients (mean +/- SEM: 73.1 +/- 6.6 letters per minute) when using their preferred hand were significantly reduced (Student's t test: P < 0.001) compared with those of healthy control subjects (mean +/- SEM: 127.7 +/- 6.4). Surface polymyography performed during writing showed 4.1-7.3 Hz rhythmic activity predominantly in the intrinsic hand and forearm muscles. Alternating, extensor activation alone, skipping from alternating to extensor activation, and co-contracting EMG patterns were recorded from the flexor and extensor muscles of the forearm. There was no evidence for excessive 'overflow' of this rhythmic EMG activity, as similar activity was detected in comparable muscle groups of healthy control subjects. Accelerometry confirmed that the frequency of PWT ranged from 4.1-7.3 Hz (median 5.5 Hz) and that normal subjects wrote with a 4.0-7.7 Hz oscillation (median 4.6 Hz). Forearm reciprocal inhibition was normal in PWT (n = 13), and thus patients with PWT can be distinguished from those with writer's cramp in whom decreased presynaptic inhibition has been found. Patients were sub-classified as having either type A (n = 11) or B (n = 10) PWT depending on whether tremor appeared during writing (type A: task induced tremor) or whilst writing and adopting the hand position used in writing (type B: positionally sensitive tremor). However, the only differences between these two groups were that a co-contracting EMG pattern and tremor induced by tendon taps to the volar aspect of the wrist were present in type B but not type A cases.

Adult↗

A study of hereditary essential tremor.

Twenty index patients with hereditary essential tremor and their kindreds were studied to define the phenotype of this condition. Ninety-three first degree and 38 more distant relatives were examined; 53 definite and 18 possible secondary cases were identified. The age of tremor onset was bimodally distributed with a median at approximately 15 years. Segregation analysis indicated autosomal dominant inheritance and penetrance was virtually complete by the age of 65 years. There were no examples of the disease skipping a generation. Men and women were affected in equal proportions. About 50% of cases were alcohol responsive. In the majority of families alcohol responsiveness was either consistently present or did not occur, but in 20% of kindreds definite heterogeneity of responsiveness was encountered within each family. The typical phenotype was a mild symmetrical postural tremor of the upper limbs. Tremor of the legs, head, facial muscles, voice, jaw and tongue occurred but never in isolation and rest, task specific (e.g. primary writing tremor) and primary orthostatic tremors were not found. Head tremor was invariably mild and 75% was of a 'no-no' type. Dystonia (e.g. torticollis and writer's cramp) were not encountered, a finding which strongly suggests that many previous studies of 'essential tremor' were contaminated by cases of idiopathic or hereditary torsion dystonia. No association with Parkinson's disease was found but classical migraine occurred in approximately 26% of cases and co-segregated with tremor. The severity of arm tremor (assessed using a clinical rating scale and by scoring tremor in Archimedes spirals) and disability increased with advancing age and increasing tremor duration, but there was no correlation between age at tremor onset and either tremor severity or disability. Men and women were affected with equal severity. The sex of the affected parent had no influence on the severity of tremor or the degree of disability experienced by an affected child. Disability commenced in the second decade and progressively increased. All the index patients and 59% of the definite secondary cases had tremor induced disabilities. Eighty-five percent of index patients and 38% of secondary cases also reported some degree of social handicap. Twenty-five percent of index patients and 12% of secondary cases had been compelled to change jobs or retire. Biological fitness was normal.

Adolescent↗

A positron emission tomography study of essential tremor: evidence for overactivity of cerebellar connections.

The origin of essential tremor is unknown. Animal models have suggested that the inferior olivary nucleus may act as a tremor generator. We used positron emission tomography to study changes in regional cerebral blood flow associated with involuntary postural tremor and passive wrist oscillation in patients with essential tremor. Activation due to voluntary wrist oscillation and arm extension without tremor was studied in normal control subjects. The essential tremor group had bilaterally increased cerebellar blood flow at rest (without tremor) compared with the control group. Involuntary postural tremor was associated with further bilateral cerebellar activation, and also contralateral striatal, thalamic, and sensorimotor cortex activation. Voluntary wrist oscillation, maintained arm extension without tremor, and passive wrist oscillation were all associated with significant ipsilateral rather than bilateral cerebellar activation. We conclude that essential tremor is associated with increased bilateral cerebellar activity both at rest and during tremor.

Adult↗

Linkage analysis with chromosome 9 markers in hereditary essential tremor.

Hereditary essential tremor (ET) is an autosomal dominant disorder with variable expression and reduced penetrance. A tremor indistinguishable from ET may be observed in patients with autosomal dominant idiopathic torsion dystonia (ITD), in which the disease locus has been mapped to 9q32-34 in some kindreds, tightly linked to the argininosuccinate synthetase (ASS) locus. We performed linkage analysis in 15 families with ET containing 60 definitely affected individuals, using dinucleotide repeat polymorphisms at the ASS locus and the Abelson locus (ABL). Cumulative lod scores were -19.5 for ASS and -10.8 for ABL at a recombination fraction of 0.01, and tight linkage to ASS was excluded individually in 11 of the families. These data indicate that the ET gene is not allelic to that causing ITD.

Adolescent↗

Assessing the impact of essential tremor on upper limb function.

We compared the impact of essential tremor on the performance of three manual tasks: drawing spirals, holding a cup full of water and a joystick-controlled tracking test. Tremor amplitude and frequency were measured by accelerometry during the tracking test, when holding the cup and whilst a standard posture was maintained. The inter-relationships between tremor amplitude, frequency and task impairment were then examined. The results showed that the amplitude and frequency of essential tremor (measured from the principal spectral peak) changed with different activities, with the mildest postural tremors changing most in frequency (by up to 4-5 Hz). The amplitude of tremor decreased in almost every case during the tasks, relative to posture, and this decrement was greatest for the most severe tremors. We also demonstrate that for practical purposes, such as routine clinical situations and therapeutic trails, the effect of essential tremor upon upper limb function can be usefully assessed by two simple complementary techniques: rating spirals and measuring the volume of water split from a cup. The impairments in carrying out these tasks and the tracking test were highly correlated with one another and also with the amplitude and frequency of postural tremor. The concept of tremor "suppressability" is introduced: the relative percentage decrease in the amplitude of a particular tremor during the performance of a specific task compared to that recorded whilst holding a standard posture.

Acceleration↗

Assessing tremor severity.

A clinical rating scale which measured the severity of tremor in 20 patients (12 with essential tremor and 8 with "dystonic" tremor) was assessed at specific anatomical sites for both inter and intra-rater reliability using four raters. The scores obtained with the scale were compared with the results of upper limb accelerometry, an activity of daily living self-questionnaire and estimates of the tremor induced impairment in writing and drawing specimens. The results show that, for the purposes of routine assessment and therapeutic trials, a clinical rating scale can produce reliable results which are a more valid index of tremor induced disability than standard postural accelerometry.

Activities of Daily Living↗