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Objectives: An initial stratification of acute whiplash patients into seven risk-strata in relation to 1-year work disability as primary outcome is presented., Design: The design was an observational prospective study of risk factors embedded in a randomised controlled study., Setting: Acute whiplash patients from units, general practitioners in four Danish counties were referred to two research centres., Participants: During a 2-year inclusion period, acute consecutive whiplash-injured (age 18-70 years, rear-end or frontal-end car accident and WAD (whiplash-associated disorders) grades I-III, symptoms within 72 h, examination prior to 10 days postinjury, capable of written/spoken Danish, without other injuries/fractures, pre-existing significant somatic/psychiatric disorder, drug/alcohol abuse and previous significant pain/headache). 688 (438 women and 250 men) participants were interviewed and examined by a study nurse after 5 days; 605 were completed after 1 year. A risk score which included items of initial neck pain/headache intensity, a number of non-painful complaints and active neck mobility was applied. The primary outcome parameter was 1-year work disability., Results: The risk score and number of sick-listing days were related (Kruskal-Wallis, p<0.0001). In stratum 1, less than 4%, but in stratum 7, 68% were work-disabled after 1 year. Early work assessment (p<0.0001), impact of the event questionnaire (p<0.0006), psychophysical pain measures being McGill pain questionnaire parameters (p<0.0001), pressure pain algometry (p<0.0001) and palpation (p<0.0001) showed a significant relationship with risk stratification., Analysis: Findings confirm previous studies reporting intense neck pain/headache and distress as predictors for work disability after whiplash. Neck-mobility was a strong predictor in this study; however, it was a more inconsistent predictor in other studies., Conclusions: Application of the risk assessment score and use of the risk strata system may be beneficial in future studies and may be considered as a valuable tool to assess return-to-work following injuries; however, further studies are needed.

Headache and facial pain are among the most common, disabling and costly disorders in Europe. Correct diagnosis and treatment is important for achieving a high quality of care. As a national organisation whose role is to educate and advocate for the needs of patients with primary headaches, the Danish Headache Society has set up a task force to develop a set of guidelines for the diagnosis, organisation and treatment of the most common types of headaches and for trigeminal neuralgia in Denmark. The guideline was published in Danish in 2010 and has been a great success. The Danish Headache Society decided to translate and publish our guideline in English to stimulate the discussion on optimal organisation and treatment of headache disorders and to encourage other national headache authorities to produce their own guidelines. The recommendations regarding the most common primary headaches and trigeminal neuralgia are largely in accordance with the European guidelines produced by the European Federation of Neurological Societies. The guideline provides a practical tool for use in daily clinical practice for primary care physicians, neurologists with a common interest in headache, as well as other health-care professionals treating headache patients. The guideline first describes how to examine and diagnose the headache patient and how headache treatment is organised in Denmark. This description is followed by individual sections on the characteristics, diagnosis, differential diagnosis and treatment of each of the major headache disorders and trigeminal neuralgia. The guideline includes many tables to facilitate a quick overview. Finally, the particular problems regarding headache in children and headache in relation to female hormones and pregnancy are described.

The mechanisms for developing long-lasting neck pain after whiplash injuries are still largely unrevealed. In the present study it was investigated whether a kyphotic deformity of the cervical spine, as opposed to a straight or a lordotic spine, was associated with the symptoms at baseline, and with the prognosis one year following a whiplash injury. MRI was performed in 171 subjects about 10 d after the accident, and 104 participated in the pain recording at 1-year follow-up. It was demonstrated that postures as seen on MRI can be reliably categorized and that a straight spine is the most frequent appearance of the cervical spine in supine MRI. In relation to symptoms it was seen that a kyphotic deformity was associated with reporting the highest intensities of headache at baseline, but not with an increased risk of long-lasting neck pain or headache. In conclusion, a kyphotic deformity is not significantly associated with chronic whiplash associated pain. Moreover, it is a clear clinical implication that pain should not be ascribed to a straight spine on MRI. We suggest that future trials on cervical posture focus upon the presence of kyphotic deformity rather than just on the absence of lordosis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Prognostic factors for chronic whiplash-associated disorder (WAD) are identified. In WAD grade I-III, 50% report neck pain after one year (30% in background population). There is a female preponderance among WAD cases. 10% develop a work disability, but no gender differences are found. Age, crash issues, magnetic resonance imaging of the neck and smooth-pursuit-neck-torsion-test are of no prognostic value. While reduced active neck mobility is associated with a 4.6 times raised risk for work disability after one year, the impact-of-event score yielded an increase in OR of 3.3, and intense pre-injury distress was associated with a 2.1 OR for pain after one year and a 2.8 OR for work disability. Intense headache/neck pain and a multitude of non-painful complaints were both associated with a 3.5 to 4.0 times raised risk of work disability after a year.

A whiplash trauma is caused by an acceleration-deceleration force transferring its energy to the cervical spine. Whiplash-associated disorder (WAD) refers to the symptoms that develop after a whiplash injury. The prognosis is favorable with recovery in over 90% of the injured subjects. In a fraction of patients, long-term symptoms with pain and cognitive and emotional symptoms may occur, causing long-term disability. The pathophysiology is unclear. Most research groups favor a multifactorial pathophysiology similar to that observed for other chronic pain conditions without a clear nociceptive or neuropathic component.

Patients with acute whiplash trauma were followed to examine if pre-collision pain and psychological distress were associated with reduced work capability and neck pain at 12 month follow-up. Pre-collision unspecified pain was associated with reduced work capability, and neck pain and pre-collision psychological distress was associated with neck pain. In conclusion unspecified pain (as opposed to specified pain) and high accumulation of pre-collision psychological distress (as opposed to a single psychological disorder) before the collision was associated with poor recovery at follow-up.

A group of clinicians from across Europe experienced in the use of botulinum toxin type A for the treatment of spasticity following acquired brain injury gathered to develop a consensus statement on best practice in managing adults with spasticity. This consensus table summarizes the current published data, which was collated following extensive literature searches, their assessment for level of evidence and discussion among the whole group. Published information is supplemented by expert opinion based on clinical experience from 16 European countries, involving 28 clinicians, who treat an average of approximately 200 patients annually, representing many thousand spasticity treatments with botulinum toxin per year.

Local sensitization to noxious stimuli has been previously described in acute whiplash injury and has been suggested to be a risk factor for chronic sequelae following acute whiplash injury. In this study, we prospectively examined the development of tender points and mechano-sensitivity in 157 acute whiplash injured patients, who fulfilled criteria for WAD grade 2 (n=153) or grade 3 (n=4) seen about 5 days after injury (4.8+/-2.3) and who subsequently had or had not recovered 1 year after a cervical sprain. Tender point scores and stimulus-response function for mechanical pressure were determined in injured and non-injured body regions at specific time-points after injury. Thirty-six of 157 WAD grade 2 patients (22.9%) had not recovered, defined as reduced work capacity after 1 year. Non-recovered patients had higher total tender point scores after 12 (p<0.05), 107 (p<0.05) and 384 days (p<0.05) relative to those who recovered. Tenderness was found in the neck region and in remote areas in non-recovered patients. The stimulus-response curves for recovered and non-recovered patients were similar after 12 days and 107 days after the injury, but non-recovered patients had steeper stimulus-response curves for the masseter (p<0.02) and trapezius muscles (p<0.04) after 384 days. This study shows early mechano-sensitization after an acute whiplash injury and the development of further sensitization in patients with long-term disability.

Patients with acute whiplash trauma were followed to examine if post-trauma ratings of pre-collision pain and psychological distress were associated with reduced work capability and neck pain at 12 months follow-up. The study included 740 consecutive patients (474 females, 266 males) referred from emergency departments or primary care after car accidents in four counties in Denmark. After the collision patients received a questionnaire on psychological distress, unspecified pain and socio-demographics and 12 months later a follow-up on work capability and neck pain was performed. Risk factors were identified by multiple logistic regression analysis. Factors associated with affected work capacity at the 12-month follow-up were pre-collision unspecified pain condition (OR=2.4, p=0.002) and socio-demographic characteristics: female gender, low educational level, unemployment and blue collar worker. Factors associated with considerable neck pain at follow-up were pre-collision unspecified pain (OR=3.5, p<0.000), pre-collision high psychological distress (OR=2.1, p=0.03) and socio-demographic characteristics: female gender and formal education >4 years. Pre-collision neck pain and severity of accident were not associated with poor outcome. In conclusion unspecified as opposed to specified pain (neck pain) before the collision is associated with poor recovery and high accumulation of pre-collision psychological distress is associated with considerable neck pain at follow-up. However, no conclusions on causality can be drawn. Personal characteristics before the collision are important for recovery and attention to pre-collision characteristics may contribute to the prevention of poor recovery after acute whiplash trauma.

Chronic whiplash-associated disorder (WAD) represents a major medical and psycho-social problem. The typical symptomatology presented in WAD is to some extent similar to symptoms of post traumatic stress disorder. In this study we examined if the acute stress reaction following a whiplash injury predicted long-term sequelae. Participants with acute whiplash-associated symptoms after a motor vehicle accident were recruited from emergency units and general practitioners. The predictor variable was the sum score of the impact of event scale (IES) completed within 10 days after the accident. The main outcome-measures were neck pain and headache, neck disability, general health, and working ability one year after the accident. A total of 737 participants were included and completed the IES, and 668 (91%) participated in the 1-year follow-up. A baseline IES-score denoting a moderate to severe stress response was obtained by 13% of the participants. This was associated with increased risk of considerable persistent pain (OR=3.3; 1.8-5.9), neck disability (OR=3.2; 1.7-6.0), reduced working ability (OR=2.8; 1.6-4.9), and lowered self-reported general health one year after the accident. These associations were modified by baseline neck pain intensity. It was not possible to distinguish between participants who recovered and those who did not by means of the IES (AUC=0.6). In conclusion, the association between the acute stress reaction and persistent WAD suggests that post traumatic stress reaction may be important to consider in the early management of whiplash injury. However, the emotional response did not predict chronicity in individuals.

Unlabelled: Whiplash injury and chronic whiplash syndrome represent major health problems in certain western communities, pain being the main symptom. Sensitization of the nociceptive system may play a role for non-recovery after whiplash injury., Aims: This study examined if tolerance to endure pain stimuli may predict outcome in whiplash injury. In a prospective fashion, 141 acute whiplash patients exposed to rear-end car collision (WAD grade 1-3) and 40 ankle-injured controls were followed and exposed to a cold pressor test, respectively, 1 week, 1, 3, 6 and 12 months after the injury. VAS score of pain and discomfort was obtained before, during and after immersion of the dominant hand into cold water for 2 min. The McGill Pain Questionnaire showed that ankle-injured controls had higher initial pain scores than the corresponding whiplash group, while whiplash-injured subjects had higher scores at 6 months; pain scores being similar at other time points. No difference was found in cold pressor pain between recovered whiplash patients and ankle-injured subjects. Non-recovery was only encountered in whiplash injury. Eleven non-recovered whiplash patients (defined as: handicap after 1 year) showed reduced time to peak pain from 1 week to 3 months (P<0.001), 6 months (P<0.01), but not 12 months after the injury. A larger pain area was seen in non-recovered vs. recovered whiplash-injured subjects during the entire observation period (P<0.001). Non-recovery after whiplash was associated with initially reduced cold pressor pain endurance and increased peak pain, suggesting that dysfunction of central pain modulating control systems plays a role in chronic pain after acute whiplash injury.

Muscle pain is often accompanied by a feeling of muscle fatigue and weakness. We examined the effect of experimental muscle pain on the electromyogram (EMG) during maximal voluntary contraction (MVC), and on the compound muscle action potential (CMAP) of the brachial biceps muscle. Twenty-one healthy subjects were injected intramuscularly with 0.1 ml/30 microg of the vanilloid receptor agonist (capsaicin) or 0.2 ml of 5% hypertonic saline. A Teflon-coated cannulated EMG needle was used to record the EMG interference pattern (IP) at MVC. The CMAP of the brachial biceps muscle was obtained by stimulation of the musculocutaneous nerve at the axilla using surface electrodes. Amplitude, mean frequency of the power spectrum, and turns/s of the interference pattern were reduced after pain induced by capsaicin or hypertonic saline. Latency, amplitude, and area-under-curve of the CMAP did not change after injection of either substance. Acute stimulation of muscle nociceptors thus produced a fatiguelike change in the interference pattern during MVC, possibly due to a decrease in motoneuron firing rate and increased muscle fatigability.

Spontaneous electrical activity, interpreted as motor endplate activity, has been reported at muscle trigger points. This study examined whether the motor endplate region, identified by electromyography, is more sensitive to noxious stimuli than other muscle sites. We induced pain in the brachial biceps muscles of 21 healthy subjects by injecting capsaicin (30 microg/0.1 ml) and NaCl (5%/0.2 ml) in the motor endplate region and at electrically silent muscle sites. Needle and evoked pain were measured by a visual analogue scale (VAS) (0-10) and the short form of the McGill Pain Questionnaire. The needle pain in the motor endplate region differed both in intensity and quality from that at other sites. The maximal pain after NaCl 5% was higher, and the VAS area-under-the-curve for NaCl 5% and capsaicin were larger, in the motor endplate region than in other sites. A higher density of muscle nociceptors in the vicinity of the motor endplate region may account for the observed differences in pain. These findings may have clinical implications for the treatment of musculoskeletal pain conditions.

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.

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.

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.