Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON): a randomised, double-blind, multicentre, phase 3, electrical dose-controlled trial.

BACKGROUND: Occipital nerve stimulation (ONS) has shown promising results in small uncontrolled trials in patients with medically intractable chronic cluster headache (MICCH). We aimed to establish whether ONS could serve as an effective treatment for patients with MICCH. METHODS: The ONS in MICCH (ICON) study is an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial. The study took place at four hospitals in the Netherlands, one hospital in Belgium, one in Germany, and one in Hungary. After 12 weeks' baseline observation, patients with MICCH, at least four attacks per week, and history of being non-responsive to at least three standard preventive drugs, were randomly allocated (at a 1:1 ratio using a computer-generated permuted block) to 24 weeks of occipital nerve stimulation at either 100% or 30% of the individually determined range between paraesthesia threshold and near-discomfort (double-blind study phase). Because ONS causes paraesthesia, preventing masked comparison versus placebo, we compared high-intensity versus low-intensity ONS, which are hypothesised to cause similar paraesthesia, but with different efficacy. In weeks 25-48, participants received individually optimised open-label ONS. The primary outcome was the weekly mean attack frequency in weeks 21-24 compared with baseline across all patients and, if a decrease was shown, to show a group-wise difference. The trial is closed to recruitment (ClinicalTrials.gov NCT01151631). FINDINGS: Patients were enrolled between Oct 12, 2010, and Dec 3, 2017. We enrolled 150 patients and randomly assigned 131 (87%) to treatment; 65 (50%) patients to 100% ONS and 66 (50%) to 30% ONS. One of the 66 patients assigned to 30% ONS was not implanted and was therefore excluded from the intention-to-treat analysis. Because the weekly mean attack frequencies at baseline were skewed (median 15·75; IQR 9·44 to 24·75) we used log transformation to analyse the data and medians to present the results. Median weekly mean attack frequencies in the total population decreased from baseline to 7·38 (2·50 to 18·50; p<0·0001) in weeks 21-24, a median change of -5·21 (-11·18 to -0·19; p<0·0001) attacks per week. In the 100% ONS stimulation group, mean attack frequency decreased from 17·58 (9·83 to 29·33) at baseline to 9·50 (3·00 to 21·25) at 21-24 weeks (median change from baseline -4·08, -11·92 to -0·25), and for the 30% ONS stimulation group, mean attack frequency decreased from 15·00 (9·25 to 22·33) to 6·75 (1·50 to 16·50; -6·50, -10·83 to -0·08). The difference in median weekly mean attack frequency between groups at the end of the masked phase in weeks 21-24 was -2·42 (95% CI -5·17 to 3·33). In the masked study phase, 129 adverse events occurred with 100% ONS and 95 occurred with 30% ONS. None of the adverse events was unexpected but 17 with 100% ONS and eight with 30% ONS were labelled as serious, given they required brief hospital admission for minor hardware-related issues. The most common adverse events were local pain, impaired wound healing, neck stiffness, and hardware damage. INTERPRETATION: In patients with MICCH, both 100% ONS intensity and 30% ONS intensity substantially reduced attack frequency and were safe and well tolerated. Future research should focus on optimising stimulation protocols and disentangling the underlying mechanism of action. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.

Validation of the accuracy of needle placement as used in diagnostic local analgesia of the maxillary nerve for investigation of trigeminally mediated headshaking in horses.

Diagnostic local anaesthesia of the maxillary nerve is a valuable aid in the diagnosis of trigeminally mediated headshaking in horses. Our objective is to validate the accuracy of needle placement in this procedure and to identify any correlation between accuracy of the technique and operator experience. Using a small volume of contrast medium, the procedure was performed bilaterally on 30 horse cadaver heads by three groups with different levels of experience with the technique. The location of deposition was then identified using computed tomography (CT). Contrast medium was deposited around the target site in 53.3% (32/60) of injections. An experienced operator succeeded in deposition around the target area significantly (p<0.05) more often (80%, 16/20) than did the less and non-experienced performers (40%, 16/40). A negative response to diagnostic local anaesthesia of the maxillary nerve does not disprove facial dysaesthesia as the cause of headshaking in that horse as a false negative response could arise due to failure to deposit local anaesthetic around the target area. Increased experience in performing the procedure decreases the probability of false negative results.

Anatomy and anaesthesia of the equine external ear canal.

Anaesthesia of the external ear canal (external acoustic meatus) is usually performed by blocking both the great and internal auricular nerves by regional infiltration. However, exact landmarks for blocking the internal auricular nerve to accomplish effective anaesthesia have not been described yet. In this study, detailed anatomical dissection of the equine external ear canal and its nerve supply was carried out on fifteen cadaver heads. Tissue samples of the dissected nerves were taken from two cadaver heads processed and were evaluated microscopically. Prior to the dissection, the region of interest was evaluated ultrasonographically, and injection of a local anaesthetic was simulated with an injection of methylene blue on ten cadaver heads. The tympanic membranes of three cadaver heads were obtained by microdissection and processed for microscopic evaluation. The entrance point of the internal auricular nerve, which is a branch of the facial nerve, into the ear canal is formed by the styloid process of the auricular cartilage. Using ultrasound, the styloid process presented as a thin hyperechoic line 2.17-2.97 cm deep, based on the skin surface. Landmarks for performing a complete and reliable anaesthesia of the external ear canal were established, and the simulated anaesthesia with methylene blue injection was evaluated as successful in all ten cases. Additionally, the histological composition of the equine tympanic membrane is described and illustrated.

Focused local anesthesia and analgesia for head and neck surgery.

Facility in the use of head and neck regional blocks will provide excellent perioperative analgesia and patient satisfaction. The scope of ambulatory surgical care for head and neck surgery will undoubtedly increase as expertize in these blocks expand in the face of strict criteria for patient selection. Supplemental sedation will be more precise with the intended result of less hangover and nausea and vomiting.

[Use of anesthesiological technologies in the complex treatment of cervicocranial pain syndromes].

Four hundred and eighty-four patients with pain syndromes of cervicocranial localization, such as migraine, exercise-induced headache, cervicogenic headache, trigeminal neuralgia, trigeminal neuropathy, and occipital neuralgia were observed. The patients were randomized by the type, intensity, and duration of the pain syndrome and subdivided into two subgroups in each of the study nosological entities. The patients from control groups received the conventional complex therapy including drug (nonsteroidal anti-inflammatory drugs, central myorelaxants, anticonvulsants, and antidepressants depending on the type of a pain syndrome) and non-drug (physiotherapy, massage, and therapeutic exercises) ones. The patients were examined before, during, and after a course of therapy and comprised neurological and neuroorthopedic examinations; pain rating by the visual-analogue and the rank scale, and neuroimaging and electrophysiologic techniques. Comparison of the results obtained in the respective subgroups has indicated that anesthetic modes and reflex exposures in the complex therapy is an effective and safe procedure for relieving pain in the head and neck. Medicinal blocks arrest pain at shorter notice, reduce the single and daily doses of the used drugs and, in some cases, avoid their administration, thus, preventing their side effects, improve the quality of life, and increase the social activity of patients with cervicocranial pain syndromes.

Can classical acupuncture points and trigger points be compared in the treatment of pain disorders? Birch's analysis revisited.

BACKGROUND: A 1977 study by Melzack et al. reported 100% anatomic and 71% clinical pain correspondences of myofascial trigger points and classical acupuncture points in the treatment of pain disorders. A reanalysis of this study's data using different acupuncture resources by Birch a quarter century later concluded that correlating trigger points to classical acupuncture points was not conceptually possible and that the only class of acupuncture points that could were the a shi points. Moreover, Birch concluded that no more than 40% of the acupuncture points examined by Melzack et al. correlated clinically for the treatment of pain (correlation was more like 18%-19%). OBJECTIVE: To examine Birch's claims that myofascial trigger points cannot conceptually be compared to classical acupuncture points and that most (at least 60%) of the classical acupuncture points examined by the study of Melzack et al. are not recommended for treating pain conditions, negating their findings of a 71% clinical pain correspondence of trigger points and acupuncture points. METHODS: Acupuncture references and literature were reviewed to examine the validity of the Birch study findings. RESULTS: Acupuncture references support the conceptual comparison of trigger points to classical acupuncture points in the treatment of pain disorders, and their clinical correspondence in this regard is likely 95% or higher. CONCLUSIONS: Although separated by 2000 years temporally, the acupuncture and myofascial pain traditions have fundamental clinical similarities in the treatment of pain disorders. Myofascial pain data and research may help elucidate the mechanisms of acupuncture's effects.

Molecular characterization of HLH-17, a C. elegans bHLH protein required for normal larval development.

The basic helix-loop-helix (bHLH) transcription factor family regulates numerous developmental events in eukaryotic cells. In the model system, C. elegans, thirty-seven bHLH proteins have been identified via genome-wide sequence analysis and fourteen have been genetically characterized to date. These proteins influence cell fate specification of neural lineages and differentiation of myogenic lineages and have distinct roles in somatic gonadogenesis. We report here on the molecular characterization of HLH-17, a protein whose putative bHLH domain is homologous to the mammalian bHLH proteins BETA3 and bHLHB5. The gene hlh-17 is transcriptionally active at all developmental stages, with the highest steady state accumulation of hlh-17 mRNA during embryogenesis. An upstream hlh-17 sequence drives expression of GFP in the sheath cells of the cephalic sensilla. Finally, animals that are defective in HLH-17 via RNAi display egg-laying defects, while those carrying null mutations in hlh-17 do not develop beyond the L2 stage and are less attracted to potassium and sodium ions. We propose that hlh-17 affects the ability of C. elegans to respond to food cues, with possible downstream effects on insulin-signaling genes involved in the normal development and reproductive viability of the worm.

Contribution of neck proprioception to subjective vertical perception among experts in physical activities and untrained women.

The purpose of this study was to investigate the influence of physical training on subjective vertical perception with the different head positions in order to explore the involving of the neck proprioception. Visual field dependence was assessed using a rod and frame test on women practising judo or dance (international level) or no specific physical activity. Tests were performed with head upright or tilted head to disturb the Z-axis egocentric reference frame. A cluster analysis determined the distribution of visual field independent (VFI) and visual field dependent (VFD) participants. The first result showed no head position effect for the group of judoists (6 degrees +/-5 degrees ; 7 degrees +/-5 degrees ) and dancers (4 degrees +/-2 degrees ; 5 degrees +/-3 degrees ) but a significant effect for untrained participants (5 degrees +/-2 degrees ; 7 degrees +/-3 degrees ): their visual vertical perception was more disturbed with tilted head than with head upright. A variability exists among experts and would necessitate further analysis. The second result showed no influence of the head position for all VFD participants, whereas for VFI participants significant difference between upright and tilted head appeared both for experts (3 degrees +/-1 degrees ; 4 degrees +/-2 degrees ) and untrained participants (3 degrees +/-1 degrees ; 5 degrees +/-2 degrees ). In this research, whatever physical activity level, the VFI participants would mainly use the Z-axis reference frame and rely on proprioceptive information. VFD among experts and VFI among untrained participants suggest that proprioceptive reference frame of neck may not provide alone according the groups an appropriate postural control.

[The most important local anesthesia in cattle: a review]. / Die wichtigsten Lokalanästhesien beim Rind: Eine Ubersicht.

Surgical interventions in cattle are frequently performed under local analgesia. Local analgesia may be carried out in the standing animal without or with slight sedation or with the animal in recumbency after deep sedation. Injection of local analgesics is less time consuming than induction and maintenance of general analgesia and is, therefore, frequently used in private veterinary practice. Precise anatomical knowledge of the nerve supply to the area to be operated is a prerequisite for the successful introduction of a local analgesia. The goal of the present review is to summarize nerve supply and indications for surgery in the area of the head, male genital tract, teat and the claws of the hind limb of cattle.

Trigger point--acupuncture point correlations revisited.

UNLABELLED: In 1977, Melzack and colleagues examined the possible correspondence of acupuncture points and trigger points for the treatment of pain. They claimed a 71% correspondence between these two classes of points. Their findings have influenced many researchers and practitioners but have not been examined since 1977. The current study explores the claim of a 71% correspondence between these two classes of points through a more extensive examination of the acupuncture literature. OBJECTIVES: To investigate the claim of a 71% correspondence of acupuncture points and trigger points for the treatment of pain. METHODS: The study involved a review of acupuncture texts published since 1977, focusing on five textbooks for the in-depth analyses and a broader range of texts for the more general analyses. RESULTS: If trigger points correspond to any class of acupuncture points it would have to be to the a shi points rather than the "channel" or "extra" points with which the 1977 study attempted to find correlation. Approximately 35% of recommended acupuncture points in the treatment of pain are distant from the site of the pain, making assumptions about the infrequency of use of distant acupuncture points for pain suspect. Sixty-one percent (61%) of the acupuncture points that the 1977 study examined for the treatment of pain are not recommended at all for the treatment of pain, and 44% are not recommended in the treatment of any problem, while only 19% of the acupuncture points are frequently recommended for pain and 20% for all conditions. For the acupuncture points that corresponded in the 1977 study, the equivalent numbers are: 60% not recommended at all for pain, 47% not recommended for anything, 18% commonly recommended for pain, and 16% commonly recommended for anything. CONCLUSION: The claimed 71% correspondence of trigger points to acupuncture points is conceptually not possible. Furthermore, even putting this conceptual problem aside, no more than 40% of the acupuncture points that the 1977 study examined could correlate for the treatment of pain, and more likely, only approximately 18%-19% correlate rather than the 71% that was claimed. However, this study found a probable correspondence of trigger points to a different class of acupuncture points, the a shi points, which appears to be an important finding. Researchers and clinicians who have assumed the conclusions of the 1977 study to be correct will need to reexamine the impact of the current findings on any claims that are dependent on the conclusions of that study.

Anatomical relevance of some acupuncture points in the head and neck region that dictate medical or dental application depending on depth of needle insertion.

Many of the acupuncture points on the face, according to classic acupuncture textbooks, could be used to treat facial pain, paralysis, and toothache. But it is not specified which acupuncture point would be effective for which tooth. Many of these points, when used for the treatment of dental pain, often fail. From an anatomical point of view, we describe which acupuncture point to use for each specific area for effective treatment of dental pain. Also, we emphasize the importance of the depth of needle insertion, especially the necessity to touch the facial bone, for effective pain treatment. When performed properly, acupuncture can be very effective for relief of dental pain.

Stimulation of the greater occipital nerve induces increased central excitability of dural afferent input.

Patients with primary headaches often report pain that involves not only the front of the head, innervated by the first (ophthalmic) division of the trigeminal nerve, but also the back of the head, innervated by the greater occipital nerve (GON) that is a branch of the C(2) spinal root. The aim of this work was to study the physiology of trigeminocervical input in a model of cranial nociception by describing a population of nociceptive neurones that receive convergent input from the supratentorial dura and the GON. Rats were anaesthetized with pentobarbital, paralysed and ventilated. The parietal dura above the middle meningeal artery was stimulated through a closed cranial window. The GON was exposed in the neck and stimulated. Recordings were made from 67 neurones (52 wide dynamic range neurones/15 nociceptive-specific-neurones) in the C(2) spinal dorsal horn, which responded to stimulation of the dura and the GON. Most neurones showed receptive fields corresponding to the first trigeminal division as well as input from C(2) skin and muscle. Neurones were recorded in superficial and deep layers of the dorsal horn. All neurones tested received input from the ipsilateral and contralateral GON (n = 5). The responses to dural stimulation were analysed before and after stimulation of the GON. Supramaximal electrical stimulation of the GON (20 s to 5 min) enhanced afferent dural input in 8/20 neurones. Application of the C-fibre activator mustard oil (MO) to the cutaneous receptive field or suboccipital muscles innervated by the GON induced an increased excitability of dural responses in 8/12 and 9/10 neurones, respectively. Stimulation of muscle afferents had a significant longer facilitatory effect than cutaneous stimulation (P < 0.05). These results show that a considerable population of neurones show convergent input from both dura as well as cervical cutaneous and muscle territories, which supports the view of a functional continuum between the caudal trigeminal nucleus and upper cervical segments involved in cranial nociception. The facilitatory effect of GON stimulation on dural stimulation suggests a central mechanism at the second order neurone level. This mechanism may be important in pain referral from cervical structures to the head and therefore have implications for most forms of primary headache.

Progressive inhibition of neuromuscular structures (PINS) technique.

Progressive inhibition of neuromuscular structures (PINS) is a technique that can be included in the osteopathic manipulative treatment repertoire. It relies on knowledge of anatomy and neuromuscular physiologic features as well as on standard forms of osteopathic palpatory diagnosis and treatment. It is a variant of the inhibition technique that has been taught as an osteopathic manipulative technique for many years, and it bears some resemblance to other manual medicine techniques. The emphasis of the approach is the determination of the alteration of the tissues due to dysfunction, delivering treatment based on palpatory evaluation and patient feedback. Two related points are initially chosen, followed by a progression from one to the other. Relationships to similar techniques are also discussed. Theoretical as well as selected practical applications are presented.

The assessment of disability caused by migraine.

Migraine is common and can be disabling. Simple systems for rating the degree of disability and assessing the prevailing migraine threshold are described. Together they are relevant in considering both the diagnosis and treatment of the condition.

Trigger points and acupuncture points for pain: correlations and implications.

Trigger points associated with myofascial and visceral pains often lie within the areas of referred pain but many are located at a distance from them. Furthermore, brief, intense stimulation of trigger points frequently produces prolonged relief of pain. These properties of trigger points--their widespread distribution and the pain relief produced by stimulating them--resemble those of acupuncture points for the relief of pain. The purpose of this study was to determine the correlation between trigger points and acupuncture points for pain on the basis of two criteria: spatial distribution and the associated pain pattern. A remarkably high degree (71%) of correspondence was found. This close correlation suggests that trigger points and acupuncture points for pain, though discovered independently and labeled differently, represent the same phenomenon and can be explained in terms of the same underlying neural mechanisms. The mechanisms that play a role in the genesis of trigger points and possible underlying neural processes are discussed.