Cephalalgia

Mục tiêu: Đây là nghiên cứu thứ hai trong cặp nghiên cứu được thiết kế để đánh giá hiệu quả và độ an toàn của onabotulinumtoxinA (BOTOX®) trong việc dự phòng đau đầu ở người lớn bị đau nửa đầu mạn tính.

Phương pháp: PREEMPT 2 là một nghiên cứu giai đoạn 3, với giai đoạn mù đôi, kiểm soát giả dược kéo dài 24 tuần, sau đó là giai đoạn mở kéo dài 32 tuần. Các đối tượng được phân bố ngẫu nhiên (1:1) để tiêm onabotulinumtoxinA (155U–195U; n = 347) hoặc giả dược (n = 358) mỗi 12 tuần trong hai chu kỳ. Tiêu chí chính của hiệu quả là sự thay đổi trung bình số ngày đau đầu mỗi 28 ngày từ cơ sở đến các tuần 21–24 sau điều trị.

Kết quả: OnabotulinumtoxinA vượt trội hơn so với giả dược một cách có ý nghĩa thống kê đối với tiêu chí chính, tần suất số ngày đau đầu mỗi 28 ngày so với cơ sở (−9.0 onabotulinumtoxinA/−6.7 giả dược, p < .001). OnabotulinumtoxinA có ưu thế đáng kể trong tất cả các so sánh tiêu chí phụ. OnabotulinumtoxinA an toàn và được dung nạp tốt, với ít tác dụng phụ liên quan đến điều trị. Một số ít bệnh nhân (3.5% onabotulinumtoxinA/1.4% giả dược) đã ngưng điều trị do tác dụng phụ.

Kết luận: Kết quả của PREEMPT 2 chứng minh rằng onabotulinumtoxinA hiệu quả để dự phòng đau đầu ở người lớn bị đau nửa đầu mạn tính. Các liệu trình onabotulinumtoxinA lặp lại an toàn và được dung nạp tốt.

Evidence from animals and humans suggests that brainstem nuclei such as the raphe nuclei, the locus coeruleus (LC) and the periaqueductal grey matter (PAG), are involved in the pathophysiology of migraine. In order to understand possible neurotransmitters involved we have, by means of indirect immunocytochemistry, analysed these regions for the occurrence and distribution of calcitonin gene-related peptide (CGRP), substance P (SP), pituitary adenylate-cyclase activating peptide (PACAP) and vasoactive intestinal polypeptide (VIP). CGRP-immunoreactive (-ir) cell bodies, but no fibres, were found to occur in high numbers, constituting 80% of all nerve cell bodies in the LC. A smaller number of these nerve cell bodies (40%) in the LC proved to be PACAP-ir. The LC neurones also stored the vesicular monoamine transporter (VMAT)- and the C-terminal flanking peptide of neuropeptide Y (C-PON)-ir, illustrating their adrenergic nature. Double immunostaining revealed that all VMAT-and C-PON-containing neurones, in addition, stored CGRP. Immunoreactive cell bodies were not seen in the nucleus raphe magnus (NRM) or PAG. Numerous SP-ir nerve fibres were observed in the NRM, the LC and the PAG. Few PACAP-ir nerve fibres were detected in the PAG and few VIP-ir nerve fibres were seen in the NRM and the PAG.

We studied the safety and efficacy of 0 U, 50 U, 100 U, 150 U (five sites), 86 Usub and 100 Usub (three sites) botulinum toxin type A (BoNTA; BOTOX^®; Allergan, Inc., Irvine, CA, USA) for the prophylaxis of chronic tension-type headache (CTTH). Three hundred patients (62.3± female; mean age 42.6 years) enrolled. For the primary endpoint, the mean change from baseline in the number of TTH-free days per month, there was no statistically significant difference between placebo and four BoNTA groups, but a significant difference favouring placebo vs. BoNTA 150 was observed (4.5 vs. 2.8 tension headache-free days/month; P = 0.007). All treatment groups improved at day 60. Although efficacy was not demonstrated for the primary endpoint, at day 90, more patients in three BoNTA groups had ≥50± decrease in tension headache days than did placebo ( P ≤ 0.024). Most treatment-related adverse events were mild or moderate, and transient. BoNTA was safe and well-tolerated in the study.

The study was aimed at developing a reference model for experimental pain and tenderness in the human temporal muscle by the local injection of hypertonic saline, potassium chloride and acidic phosphate buffer, using isotonic saline as control. The design was randomized and double-blind. Twenty healthy subjects had 0.2 ml test solution injected into one temporal muscle and saline into the other. Following each injection, pain was rated on a 10-point ordinal scale and pressure-pain thresholds were measured every minute for 10 min by a pressure algometer. Hypertonic saline ( n = 11) and potassium chloride ( n = 12) induced significantly more pain than isotonic saline ( ANOVA, p < 0.0001). Compared to control injections, hypertonic saline and potassium chloride induced a significant reduction in pressure-pain threshold (ANOVA, p < 0.0001 and p < 0.05). Forty-eight percent of the injections led to the referral of pain most often to the jaws. A positive correlation between the relative occurrence of referred pain and pain intensity was observed ( p < 0.001) as was a negative correlation between the decrease in pressure-pain threshold and pain intensity ( p < 0.05).

After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.

Cluster headache is perhaps the most painful of the primary headache disorders. Its treatment includes acute, transitional, and preventive therapy. Despite the availability of many treatments, cluster headache patients can still be difficult to treat. We treated 14 cluster headache patients with greater occipital nerve block as transitional therapy (treatment initiated at the same time as preventive therapy). The mean number of headache-free days was 13.1+23.6. Four patients (28.5%) had a good response, five (35.7%) a moderate, and five (35.7%) no response. The greater occipital nerve block was well tolerated with no adverse events. Headache intensity, frequency and duration were significantly decreased comparing the week before with the week after the nerve block ( P< 0.003, P = 0.003, P< 0.005, respectively). Greater occipital nerve blockade is a therapeutic option for the transitional treatment of cluster headache.

The origins of chronic headache and the role of the greater occipital nerve in headache syndromes are reviewed. The anatomical pathways and physiological basis of these headaches are discussed with a view to synthesizing some current concepts of headache generation. Studies of occipital nerve blockade for treatment of headaches of various types are assessed and a retrospective analysis of our own experience is presented.