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The use of botulinum neurotoxin-A (BoNT-A) is an alternative for the management of orofacial pain disorders. Although only Botox has labeled, there are other commercial brands available for use, among them: Dysport, Botulift, Prosigne, and Xeomin. The objective of the present study was to evaluate the possible differences in the antinociceptive effect evoked by different commercially available formulations of BoNT-A in an animal model of inflammatory orofacial pain induced by formalin injection. Male C57/BL6 mice (20–25 g) were submitted to the pre-treatment with five different commercial brands of BoNT-A (Botox, Botulift, Xeomin, Dysport, or Prosigne; with doses between 0.02 and 0.2 Units of Botulinum Toxin, in 20 μL of 0.9% saline) three days prior the 2% formalin injection. All injections were made subcutaneously into the right perinasal area. After formalin injections, nociceptive behaviors like rubbing the place of injection were quantified during the neurogenic (0–5 min) and inflammatory (15–30 min) phases. The treatment using Botox, Botulift, and Xeomin were able to induce antinociceptive effects in both phases of the formalin-induced pain animal model, however, Dysport and Prosigne reduced the response in neither of them. Our data suggest that the treatment using different formulations of BoNT-A is not similar in efficacy as analgesics when evaluated in formalin-induced orofacial pain in mice., Graphical abstract Image 1, Highlights • Botulinum neurotoxin-a reduced formalin-induced orofacial pain in mice. • There are differences in the analgesic potential of different available commercial brands of botulinum neurotoxin-A. • Botox, Botulift, Xeomin demonstrated analgesic effect when evaluated in formalin-induced orofacial pain in mice.

Objective: To characterise the clinical features of non-familial migraine with unilateral motor symptoms (MUMS) and compare these features with those of migraine without weakness. Methods: 24 patients with MUMS and 48 matched controls were identified from a tertiary care headache centre. Using a structured interview, the migraine symptoms of both groups were characterised. Results of previously administered Beck Depression Inventories (BDI), Minnesota Multiphasic Personality Inventories and psychiatric diagnoses were collected, when available, and compared between groups. Results: 9 patients had episodic migraine and 15 had chronic migraine. Patients with MUMS always had weakness involving the arm subjectively, and both arm and leg objectively. A give-way character was always present. Only 17% of patients with MUMS reported facial weakness; 58% reported persistent interictal weakness; 92% reported sensory symptoms. A rostrocaudal march of sensory and motor symptoms was frequently reported. Weakness was ipsilateral to unilateral headache in two thirds of the patients. Compared with controls, patients with MUMS had had similar pain intensities, but were more likely to report other migrainous symptoms, including allodynia. 38% of patients with MUMS were told they had had a stroke, and 17% believed they had had a stroke despite normal brain imaging. Patients with MUMS reported fewer affective disorders and more adjustment disorders than controls, and had similar BDI scores. Conclusions: A syndrome of severe migraine with accompanying give-way weakness is common in tertiary care headache centres. It is accompanied by other neurological symptoms.

Objectives: Migraine has been identified as an independent risk factor for ischemic stroke. Both neurogenic inflammation and platelet activation have been linked to the pathophysiology of migraine. Increased platelet activation results in up-regulation of specific binding to leukocytes which promotes pro-inflammatory leukocyte secretion and their tethering to endothelium, a mechanism that has been demonstrated in stroke and which could provide a link to migraine. We aimed to determine whether platelet–leukocyte aggregation is increased in migraine patients outside an acute attack. Methods: Seventy two patients with migraine according to IHS criteria were compared to a control group (n = 72). Whole blood flow cytometry was used to quantify the activation dependent P selectin on the platelet, and to assess the fraction of platelets bound to the different leukocyte subsets. Results: Migraine patients showed significantly more platelet–leukocyte aggregates compared to the control subjects (p = 0.003). This effect was driven by an increased polymorphonuclear cell–platelet aggregation (p = 0.003) whereas platelet aggregation with monocytes and lymphocytes was not. Platelet activation was also increased (p = 0.001). Conclusions: In migraine pro-inflammatory platelet adhesion to leukocytes occurs during the headache free interval similar to that seen in acute coronary and cerebrovascular syndromes. This may suggest a link between migraine and stroke on a cellular level.

Background: Cluster headache (CH) is a relatively rare disease and episodic CH is more frequent than chronic CH. Few studies have described the characteristics of patients with chronic CH. Methods: This was a descriptive study carried out by eight tertiary care specialist headache centres in France participating in the Observatory of Migraine and Headaches (OMH). From 2002 to 2005, OMH collected data from 2074 patients with CH, of whom 316 had chronic CH. From January to June 2005, 113 patients with chronic CH were interviewed using standardised questionnaires during a consultation. Results: The male to female ratio was 4.65:1. Median age was 42 years. The majority of patients were smokers or former smokers (87%). 46% had primary chronic CH (chronic at onset) and 54% secondary chronic CH (evolving from episodic CH). Most patients had unilateral pain during attacks and 7% had sometimes bilateral pain during an attack. 48% reported a persisting painful state between attacks. Symptoms anteceding pain onset (mainly discomfort/diffuse pain, exhaustion, mood disorders) and auras were reported by 55% and 20% of patients, respectively. The functional impact of chronic CH was estimated as severe by 74% of patients, and 75.7% suffered from anxiety, as assessed by the Hospital Anxiety and Depression scale. There was no substantial difference in clinical presentation between primary and secondary CH. Discussion: This study confirms the existence of auras and interictal signs and symptoms in patients with chronic CH, and male sex and smoking as CH risk factors. Primary and secondary chronic CH appear equally prevalent. Male sex does not appear to favour the shift from episodic to chronic CH.

Objectives: Since 1998, migraine with aura (MA) has been diagnosed according to the operational diagnostic criteria of the International Headache Society (ICHD-1). Here we present the data underlying the new criteria for MA in the ICHD-2 classification. Methods: Sensitivity of the new criteria was tested in patients with MA and specificity in patients with reversible non-aura visual disturbances. The diagnoses in both groups of patients were made in a validated semistructured physician-conducted interview. We tested five sets of criteria for sensitivity and specificity comparing with the diagnosis according to the ICHD-1 in 200 patients and the selected set of criteria in 274 additional patients. Results: Four sets of criteria had sensitivity/specificity of 46%/100%, 71%/100%, 62%/95%, and 99%/76%. Sensitivity of the selected set of criteria was 84% (95% CI 79% to 90%) and specificity 97% (95% CI 95% to 99%). According to these criteria at least two of the following should be fulfilled: homonymous visual or unilateral sensory symptoms; at least one aura symptom develops gradually over ⩾5 minutes and/or different symptoms occur in succession over ⩾5 minutes; each symptom lasts ⩾5 and ⩽60 minutes. In the additional sample sensitivity of the selected criteria was 90% (95% CI 86% to 94%) and specificity 96% (95% CI 91% to 100%). Conclusions: The diagnostic criteria for MA selected for ICHD-2 had high sensitivity and specificity. The ICHD-2 criteria are more operational and probably delineate a more homogeneous sample of patients than the ICHD-1. The ICHD-2 for MA is intended equally for research and clinical practice and can be used at different levels of specialisation.

Objective: To determine the agreement between lay interviewers and experts in the diagnosis of migraine by questionnaire. Subjects: A population based sample of 1188 individuals aged 64 to 73 years. Methods: Participants who declared that they had recurrent headaches (n = 238) answered a structured questionnaire by lay interviewers with special training in migraine. A migraine expert subsequently interviewed all the headache sufferers using the same questionnaire. Migraine was defined according to the International Headache Society criteria. Results: In comparison with the expert, the diagnosis derived by the lay interviewers had high values for specificity (97%) and positive predictive value (86%), and a low sensitivity (50%) and negative predictive value (57%). Agreement between the expert and the lay interviewers was low, with a κ value of 0.36 (95% confidence interval 0.26 to 0.47). The most serious discrepancies concerned the duration of attacks, the worsening of headaches by physical activity, the presence of nausea or vomiting, and the unilaterality of headaches. As a result, the lifetime prevalence of migraine headaches was greatly underestimated by lay interviewers (6.5%) in comparison with the expert (11.1%). Conclusions: A low level of agreement between lay interviewers and a headache expert in the diagnosis of migraine headaches by structured questionnaire may result in a substantial underestimation of migraine prevalence.

Objectives: To determine if physical and/or psychological risk factors could differentiate between subtypes of primary headache (migraine, tension-type headache (TTH), and coexisting migraine and TTH (combined)) among members of a longitudinal birth cohort study. Methods: At age 26, the headache status of members of the Dunedin Multidisciplinary Health and Development Study (DMHDS) was determined using International Headache Society criteria. Headache history and potential physical and psychological correlates of headache were assessed. These factors included perinatal problems and injuries sustained to age 26; and behavioural, personality, and psychiatric disorders assessed between ages 5 to 21. Results: The 1 year prevalences for migraine, TTH, and combined headache at the age of 26 were 7.2%, 11.1%, and 4.3%, respectively. Migraine was related to maternal headache, anxiety symptoms in childhood, anxiety disorders during adolescence and young adulthood, and the stress reactivity personality trait at the age of 18. TTH was significantly associated with neck or back injury in childhood (before the age of 13). Combined headache was related to maternal headache and anxiety disorder at 18 and 21 only among women with a childhood history of headache. Headache status at the age of 26 was unrelated to a history of perinatal complication, neurological disorder, or mild traumatic head injury. Conclusions: Migraine and TTH seem to be distinct disorders with different developmental characteristics. Combined headache may also have a distinct aetiology.