Detecting peripheral motor nervous system involvement in chronic spinal cord injury using two novel methods: MScanFit MUNE and muscle velocity recovery cycles.

OBJECTIVE: To examine the peripheral nervous system (PNS) in spinal cord injured (SCI) patients using two novel methods: (1) MScanFit MUNE; a motor unit number estimation method detecting motor unit loss and (2) muscle velocity recovery cycles (MVRCs) measuring muscle membrane properties which has previously shown depolarization of the muscle membrane in denervated muscles. METHODS: Thirty chronic SCI patients (lesion above Th10) and twenty-five gender -and age matched healthy controls (HC) were examined. MScanFit was recorded from peroneal nerve to anterior tibial muscle (TA) and tibial nerve to abductor hallucis muscle after excluding localized mononeuropathies. MVRCs were recorded from TA. RESULTS: Nerve conduction studies showed mononeuropathy in 8 patients (27%) (sciatic (2), -or peroneal nerve (6)). SCI patients had in average reduced motor unit number compared with HC and prolonged muscle refractory period and reduced supernormality. SIGNIFICANCE: A high prevalence of nerve lesion and a diffuse affection of the PNS following SCI are highly relevant findings that should be accounted for when planning neurorehabilitation for persons living with SCI.

Muscle velocity recovery cycles in neurogenic muscles.

OBJECTIVE: To examine muscle membrane properties in neurogenic muscles using Muscle Velocity Recovery Cycles (MVRCs). METHODS: Forty-seven patients referred to Nerve Conduction Studies (NCS) and Electromyography (EMG) for peroneal nerve entrapment neuropathy were prospectively included. The patients were categorized as peroneal nerve entrapment neuropathy across knee (n = 22), L5-radiculapathy (n = 10), normal NCS/EMG (n = 9) and other disorders (n = 6) using NCS/EMG and neuroimaging results. Strength in anterior tibial muscle was measured by Medical Council Scale (MRC) and disease duration was recorded. In addition to conventional NCS/EMG, all subjects were examined with MVRCs in anterior tibial muscle. This provided parameters of muscle relative refractory period (MRRP) and early supernormality (ESN) and late supernormality (LSN). The results were compared with 29 age-matched healthy control subjects. RESULTS: MRRP was prolonged and ESN and LSN were reduced in neurogenic muscles. MRRP, ESN and LSN correlated to MRC and incidence of spontaneous activity but not to motor unit potential parameters or disease duration. CONCLUSIONS: MVRC changes provide in vivo evidence of depolarization in intact human muscle fibres that could underlie reduced muscle excitability and hence weakness in neurogenic muscles. SIGNIFICANCE: MVRCs appear to be a useful technique for revealing disease mechanism in a broad range of neuromuscular diseases.

Effect of training on corticomotor excitability in clinical neck pain.

BACKGROUND: Corticomotor excitability has been shown to correlate with motor learning and functional recovery. The aim of the present study was to monitor changes in excitability of the corticomotor pathways induced by neck training and to compare the effects in patients with neck or knee pain and pain-free participants. METHODS: Corticomotor excitability was assessed using transcranial magnetic stimulation and electromyography at baseline, after 30 min and 1 h, and at a 1-week follow-up visit. The primary outcome measures were changes in amplitudes and latencies of motor evoked potentials (MEPs) at 1-week follow-up. RESULTS: MEP responses induced by neck training yielded significantly different outcomes in the three groups. In the group with neck pain and training, MEP amplitudes were significantly reduced between baseline and 30 min (p ≤ 0.05), but with no significant difference between baseline, 1 h (p = 0.178) and 1 week (p = 0.067). In the group with knee pain and training, MEP amplitudes significantly increased between baseline and 30 min (p ≤ 0.01) and 1 h (p < 0.001), but not after 1 week (p = 0.524) compared with baseline. In the pain-free group, there were no changes over time. CONCLUSION: Neck training reduced neuroplastic responsiveness of corticomotor pathways in neck pain patients in contrast to knee pain patients and pain-free participants. Increased attention to adaptive and maladaptive neuroplastic responses induced by training may prove valuable in the process of optimizing clinical outcomes.

Are there gender differences in coping with neck pain following acute whiplash trauma? A 12-month follow-up study.

BACKGROUND: Little is known about gender differences in coping after whiplash, and to date possible interaction of gender and coping on recovery has not been investigated. AIMS: To examine if gender differences in coping are associated with long-lasting neck pain after acute whiplash. Seven hundred and forty participants referred from emergency departments or general practitioners after car accidents in Denmark. Within a median of five days, post-collision participants completed questionnaires on collision characteristics, psychological distress, and socio-demographics. After 3 months they completed the Coping Strategies Questionnaire, and after 12 months a VAS scale on neck pain intensity. RESULTS: The odds for long-lasting neck pain were more than twice as high for women than for men (OR = 2.17 (95% CI: 1.40; 3.37). However, no gender difference in coping and no interaction between gender and the five coping subscales on neck pain after 12 months were found. 'Distraction' increased the odds for considerable neck pain for both men and women (OR = 1.03 (95% CI: 1.01; 1.05), 'reinterpreting' (OR = 1.03 (95% CI: 1.01; 1.06), 'catastrophizing' (OR = 1.14 (95% CI: 1.10; 1.18), and 'praying and hoping' (OR = 1.10 (95% CI: 1.05; 1.13) for each point on these scales. CONCLUSIONS: No interaction between coping and gender on neck pain was found, thus different coping strategies 3 months post-collision did not explain the different prognosis observed in men and women. Clinically relevant influence of 'catastrophizing' and 'praying and hoping' to prognosis was found, therefore we should identify patients predominantly using these strategies.

Clinical assessment of prognostic factors for long-term pain and handicap after whiplash injury: a 1-year prospective study.

BACKGROUND AND PURPOSE: Physical mechanisms are the possible factors involved in the development and maintenance of long-term handicaps after acute whiplash injury. This study prospectively examined the role of active neck mobility, cervical and extra-cervical pains, as well as non-painful complaints after a whiplash injury as predictors for subsequent handicap. METHODS: Consecutive acute whiplash patients (n = 688) were interviewed and examined by a study nurse after the median of 5 days after injury, and divided into a high- or a low-risk group by an algorithm based on pain intensity, number of non-painful complaints and active neck mobility [active cervical range of motion (CROM)]. All 458 high-risk patients and 230 low-risk patients received mailed questionnaires after 3, 6 and 12 months. Two examiners examined all high-risk patients (n = 458) and 41 consecutive low-risk patients at median 11, 109, 380 days after injury. The main outcome measures were: handicaps, severe headaches, neck pain and neck disability. RESULTS: The relative risk for a 1-year disability increased by 3.5 with initial intense neck pain and headaches, by 4.6 times with reduced CROM and by four times with multiple non-painful complaints. CONCLUSION: Reduced active neck mobility, immediate intense neck pain and headaches and the presence of multiple non-painful complaints are the important prognostic factors for a 1-year handicap after acute whiplash.

A double-blind, controlled study of botulinum toxin A in chronic myofascial pain.

BACKGROUND: Recent studies have reported a potential analgesic effect of botulinum toxin A (BTXA) in musculoskeletal pain. The present double-blind, randomized, placebo-controlled, parallel clinical trial studied the effect of BTXA on pain from muscle trigger points and on EMG activity at rest and during voluntary contraction. METHODS: Thirty patients with trigger points in the infraspinatus muscles received either 50 units/0.25 mL of BTXA or 0.25 mL of isotonic saline. Baseline measures were determined during a run-in period of 1 week. Outcome measures including local and referred spontaneous pain, pain detection and tolerance thresholds to mechanical pressure, and shoulder movement were assessed at 3 and 28 days after injection. The interference pattern of the EMG during maximal voluntary effort of infraspinatus muscle was recorded and a standardized search for spontaneous electrical motor endplate activity at the trigger points was performed before and 28 days after BTXA or saline injection. RESULTS: BTXA reduced motor endplate activity and the interference pattern of EMG significantly but had no effect on either pain (spontaneous or referred) or pain thresholds compared with isotonic saline. CONCLUSIONS: The results do not support a specific antinociceptive and analgesic effect of botulinum toxin A.

Distribution of 16alpha-[18F]fluoro-estradiol-3,17beta-disulfamate in rats, tumour-bearing mice and piglets.

Based on a high affinity to the enzyme estrone sulfatase (ES), 16alpha-[18F]fluoroestradiol-3,17beta-disulfamate ([18F]FESDS) has been suggested as a potential PET radiotracer for imaging steroid-dependent breast tumours. The distribution of [18F]FESDS was studied in rats, tumour-bearing nude mice and piglets. In all species evidence for binding to a second target, the enzyme carbonic anhydrase (CA), was obtained. ES and CA inhibitors significantly reduced the radiotracer uptake in various organs but not in tumours. It is concluded that [18F]FESDS binds to ES and CA in vivo but this binding is not strong enough to allow tumour imaging with positron emission tomography (PET).

Distribution of estrone sulfatase in rat brain determined by in vitro autoradiography with 16alpha-[18F]fluoroestradiol-3,17beta-disulfamate.

16Alpha-fluoroestradiol-3,17beta-disulfamate (FESDS) strongly inhibits estrone sulfatase (ES), an enzyme which is also present in the brain. The enzyme is probably involved in important regulatory functions of neurosteroids which may be disturbed in certain brain diseases. In the present study, [18F]FESDS was used to measure the amount of ES in various rat brain regions using quantitative in vitro autoradiography. The obtained values vary between 0.29 pmol (mg protein)(-1) (pons) and 11.5 pmol (mg protein)(-1) (striatum). They are positively correlated with the enzyme activity measured in homogenates of the corresponding regions. Because this radiotracer binds also to carbonic anhydrase in the brain it is only of limited use for in vivo imaging studies.

Has basic research contributed to chronic pain treatment?

Our understanding of nociceptive processing and of plastic changes after persistent noxious input has increased immensely within the last two decades. It is now clear that long-lasting noxious stimulation or damage to the nervous system give rise to a neuronal hyperexcitability and that this sensitisation of the nervous system plays an important role for development and maintenance of chronic pain. The manifestations of such hyperexcitability are numerous and include among others: increased neuronal response to a suprathreshold stimulus, expansion of the peripheral areas from where a central neurone can be activated and the recruitment of previous non-responding nociceptive neurones. Furthermore, it has been possible to modulate this neuronal hyperexcitability by the discovery of molecular targets for pain, by sequencing DNA of ion channels and receptors and by development of new molecules that exert their effects on these molecular targets. The changes in responsiveness appear to be partly time and intensity dependent and partly dependent on the cause of injury. Whereas relatively short-lasting and moderate noxious input leads to reversible plastic changes, more intense and long-lasting noxious stimulation implies a risk for persistent and more profound alterations in transmitters, receptors, ion channels and in neuronal connectivity. Despite the explosion of new knowledge in pain processing and in molecular background for neuroplasticity, this progress has unfortunately not resulted in a corresponding improvement of our ability to treat chronic pain. The number of patients with chronic unrelieved pain is still high and newer types of treatment have so far not resulted in a substantially better treatment. Nevertheless, there is now an ongoing systematic research in which chronic pain conditions are assessed in a fashion so that mechanisms underlying pain can be dissected. Moreover, controlled clinical trials together with systematic reviews are carried out which in the future should permit formulation of treatment algorithms for chronic pain. Finally, it is likely that the development of new specific types of treatment will show efficacy if they are evaluated and analysed not on the global pain experience, but more specifically on those targets and elements of the pain experience they are aimed to deal with.

Automated synthesis of 16alpha-[18F]fluoroestradiol-3,17beta-disulphamate.

After 16alpha-[15F]fluoroestradiol ([18F]FES) has been successfully prepared in an automated module, the synthesis of 16alpha-[18F]fluoroestradiol-3,17beta-disulphamate ([18F]FESDS) is described as a module-assisted one-pot procedure which can provide 10GBq [18F]FESDS with a radiochemical purity better than 99%. The procedure is reliable and reproducible and requires a time of about 90 min. Because of its high sulphatase-inhibitory effect [15F]FESDS is thought to be a new PET tracer to image sites of high sulphatase activity.

Pain thresholds and tenderness in neck and head following acute whiplash injury: a prospective study.

UNLABELLED: OBJECTIVE OF THE INVESTIGATION: In a 6-month prospective study of 141 consecutive acute whiplash-injured participants, and 40 acute, ankle-injured controls, pain and tenderness in the neck/head, and at a distant control site, were measured. BASIC PROCEDURES: Muscle palpation and pressure algometry in five head/neck muscle-pairs were performed after 1 week and 1, 3 and 6 months after injury. Algometry was performed at a distant control site. MAIN FINDINGS: Whiplash-injured patients had lowered pressure-pain-detection thresholds and higher palpation-score initially in the neck/head, but the groups were similar after 6 months, and the control site was not sensitized. PRINCIPAL CONCLUSION: Focal, but not generalized, sensitization to musculoskeletal structure is present until 3 months, but not 6 months, after whiplash injury, and probably does not play a major role in the development of late whiplash syndrome. Pressure algometry and palpation are useful clinical tools in the evaluation of neck and jaw pain in acute whiplash injury.

Headache, neck pain, and neck mobility after acute whiplash injury: a prospective study.

STUDY DESIGN: A 6-month prospective study of neck mobility in patients with acute whiplash injury and a control group with acute ankle distortion was conducted. OBJECTIVES: To assess active neck mobility after acute whiplash and ankle distortion injuries, and to relate neck mobility to headache, neck pain, and speed of car at the time of collision. SUMMARY OF BACKGROUND DATA: A major problem after whiplash injury is restriction of neck mobility immediately subsequent to trauma. It is, however, unclear whether neck mobility changes after the acute injury are related to the associated headache and neck pain. METHODS: Cervical range of neck motion, neck pain, and headache were assessed after 1 week, then 1, 3, and 6 months after injury in 141 patients with acute whiplash injury, and in 40 patients with acute nonsport ankle distortion. RESULTS: Patients with whiplash injury had significantly reduced flexion, extension, lateral flexion, and rotation of the neck immediately after injury, as compared with patients with ankle distortion injury. Neck mobility, however, was similar in the two groups after 3 months. In patients with whiplash injury, neck pain and neck mobility were found to be related inversely to reported headache and neck mobility. Neck mobility was not significantly related to a difference in car speed at the time of collision. CONCLUSIONS: Neck mobility is reduced immediately after, but not 3 months after, a whiplash trauma. Headache and neck mobility are related inversely and neck pain and neck mobility are related inversely during the first 6 months after acute whiplash injury.

Handicap after acute whiplash injury: a 1-year prospective study of risk factors.

BACKGROUND: Exposure to a whiplash injury implies a risk for development of chronic disability and handicap, with reported frequencies ranging from 0% to 50% in follow-up studies. The exact risk for development of chronic whiplash syndrome is not known. OBJECTIVE: To prospectively determine the sensitivity and specificity of five possible predictors for handicap following a whiplash injury. METHODS: In a 1-year prospective study of persons with acute whiplash injury (n = 141) and control subjects who had acute ankle distortion (n = 40), pain intensity, number of nonpainful neurologic complaints, cervical mobility, workload during extension and flexion of the neck, and results of psychometric assessment were recorded. The consecutively sampled injured persons were assessed with structured and semistructured questionnaires, and underwent neurologic examination after 1 week and 1, 3, 6, and 12 months. After 3 to 4 years, participants with whiplash injury were questioned about legal issues. RESULTS: After 1 year, 11 (7.8%) persons with whiplash injury had not returned to usual level of activity or work. The best single estimator of handicap was the cervical range-of-motion test, which had a sensitivity of 73% and a specificity of 91% (p < 0.01, Cox regression analysis). Accuracy and specificity increased to 94% and 99% when combined with pain intensity and other complaints. This increase was gained at the expense of a reduced sensitivity. Initiation of lawsuit within first month after injury did not influence recovery. CONCLUSION: The cervical range-of-motion test has a high sensitivity in prediction of handicap after acute whiplash injury. The value of cervical range-of-motion test is further improved by additional recording of symptoms and pain intensity.

[Multiple system atrophy--a neurodegenerative disease entity]. / Multipel system-atrofi--en neurodegenerativ sygdomsenhed.

Multiple system atrophy (MSA) is a nosological entity. Main clinical manifestations are parkinsonism, pyramidal signs, cerebellar signs and autonomic dysfunction. Postmortem studies of patients who while alive were diagnosed as having idiopathic Parkinson's disease show approximately 8% as having MSA at autopsy. Specific pathological findings are glial cytoplasmatic inclusions. It seems likely that patients with MSA are misdiagnosed or underrecognized. This review is an attempt to elucidate upon clinical and paraclinical approaches to MSA and to depict relevant research in this field. The aetiology is unknown.

Preparation of 3-ketodesogestrel metabolites by microbial transformation and chemical synthesis.

Specific microbial reactions were used for the preparation of metabolites of 3-ketodesogestrel (13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one, the active from of the progestagen desogestrel. Clostridium paraputrificum transformed 3-ketodesogestrel (KDG) to the 5 beta-dihydro and tetrahydro metabolites 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yn-3-one and 13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol, respectively. The epimeric compound 13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 beta, 17 beta-diol was obtained by chemical reduction of the 3-oxo compound. Mycobacterium smegmatis converted KDG to metabolites of the 5 alpha H-series: 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yn-3-one, 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol and 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 beta, 17 beta-diol. The ring A-aromatized analog of KDG 13-ethyl-11-methylene-18,19-dinor-17 alpha-pregna-1,3,5(10)-trien-20-yne-3,17 beta-diol was obtained by microbial 1-dehydrogenation with Rhodococcus rhodochrous. Additionally, chemical syntheses of the microbially obtained KDG metabolites listed above were carried out. These included Birch reduction, reduction of KDG with sodium borohydride in aqueous pyridine and in methanol, reduction of KDG with potassium selectride in tetrahydrofuran, and dehydrogenation of KDG with cupric-II bromide in acetonitrile. The problems encountered in chemical syntheses favor the microbial procedures. The compounds were characterized by mass spectra (MS), IR, and circular dichroism (CD). Complete assignments of 1H and 13C chemical shifts were made using homo- and heteronuclear 2-DN-NMR spectroscopy. Chromatographic [gas-liquid chromatography (GLC), high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC)] data of all the prepared KDG metabolites are presented.