L-5-Hydroxytryptophan versus placebo in childhood migraine prophylaxis: a double-blind crossover study

L-5HTP was tested versus placebo in a double-blind crossover study of 27 migraine children aged 6-12 years, who recorded their headaches in a headache diary for 1 month. Twenty-one patients subsequently started the trial. The mean daily dose of L-5HTP was 5 mg/kg body weight, and each treatment period with either L-5HTP or placebo lasted 12 weeks. In group A (L-5HTP-placebo; 10 patients) and group B (placebo-L-5HTP; 11 patients) both L-5HTP and placebo led to a significant reduction of the migraine index and frequency of migraine attacks during the 3rd month of each treatment period. However, we found a treatment X period interaction because the efficacy determinants decreased significantly during the first and the second treatment periods in both groups irrespective of the sequence of treatments. No differences were found between L-5HTP (first period of group A) and placebo (first period of group B).     

Effects of L-5HTP with and without carbidopa on plasma ß-endorphin and pain perception

L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxy-tryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator for pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) higher than that after L-5HTP alone. Neither subjective pain threshold and tolerance nor RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.     

Effects of L-5HTP with and without carbidopa on plasma β-endorphin and pain perception: possible implications in migraine prophylaxis

L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxytryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator of pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) greater than that induced by L-5HTP alone. Neither the subjective pain threshold and tolerance nor the RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.     

Central serotonergic stimulation of aldosterone secretion.

Serotonin stimulates aldosterone secretion both in vitro and in vivo, and serotonin antagonism decreases plasma aldosterone levels in patients with idiopathic aldosteronism. This study was designed to assess the effects of the serotonin precursor, 5-hydroxytryptophan (5HTP), upon aldosterone secretion in man, and to determine whether stimulatory effects of 5HTP are mediated through the central nervous system. Oral 5HTP, administered as a single 200-mg dose, increased plasma aldosterone levels from 4.7 +/- 0.6 to 13.3 +/- 2.8 ng/dl in dexamethasone-pretreated, normal volunteers. Peripheral inhibition of decarboxylation of 5HTP, achieved by pretreatment with carboxydopa, 25 mg three times daily for 3 d, significantly increased the stimulatory effects of 5HTP on aldosterone levels (P less than 0.001). No change in aldosterone levels occurred in subjects who received placebo after pretreatment with dexamethasone and carboxydopa. Increased aldosterone was not accompanied by increases in plasma levels of renin activity, potassium, or ACTH. Plasma levels of 5HTP were markedly increased by carboxydopa pretreatment, but peak plasma levels of serotonin were not significantly altered. Four patients with idiopathic aldosteronism all had an increase in plasma aldosterone levels after 5HTP administration, whereas the response in four patients with aldosterone-producing adenoma was variable. Incubation of isolated human and rat adrenal glomerulosa cells with serotonin resulted in increased aldosterone secretion by both sets of cells, whereas 5HTP was ineffective in stimulating aldosterone secretion in vitro. We conclude that central serotonergic pathways are involved in the stimulation of aldosterone induced by administration of 5HTP. This mechanism may be an important etiologic factor in the hypersecretion of aldosterone that occurs in patients with idiopathic aldosteronism.     

Effectiveness of nasal sumatriptan in 5- to 12-year-old children

OBJECTIVE: To assess the tolerability and effectiveness of nasal sumatriptan in the treatment of migraine in 5- to 12-year-old children. BACKGROUND: Although headaches are a common disorder and occur in up to 10.6% of children, many of the new migraine abortive agents have not been well evaluated in this population. It has recently been reported that nasal sumatriptan is effective in the treatment of migraine in adolescents. In younger children, it is yet to be characterized. In addition, many children have significant amounts of vomiting with their migraines, limiting their use of oral medications. DESIGN AND METHODS: Children with headache were evaluated by a child neurologist, child psychologist, and pediatric nurse practitioner. Clinical and International Headache Society diagnoses were established for each child. Patients with headaches that were either unresponsive to oral medications or had significant vomiting were treated with nasal sumatriptan. Initial administration and tolerability were performed in the Headache Center at Cincinnati's Children's Hospital Medical Center. Patients or their parents were contacted to assess the overall effectiveness of nasal sumatriptan after home administration. RESULTS: Ten patients aged between 5 and 12 years (mean, 9.9 years) received either a 5-mg (n = 2) or 20-mg (n = 8) dose of sumatriptan. All 10 patients had a clinical diagnosis of migraine; 7 met the International Headache Society criteria for migraine. The mean age of headache onset was 6.6 years. A total of 57 headaches were treated; 47 (82.5%) responded to sumatriptan. Of the patients who treated headaches, the mean number of headaches treated was 5.2, while the mean number of responsive headaches was 4.3. One patient had no response, 2 patients had a 50% response, and 6 patients had 100% response to the nasal sumatriptan. Three patients reported persistent "bad taste." CONCLUSIONS: This report demonstrates that nasal sumatriptan may be effective in aborting migraine in young children (aged 5 to 12 years). It also suggests that there may be subgroups for which it works well. This information suggests that double-blind, placebo-controlled studies are necessary to determine the overall effectiveness of nasal sumatriptan in this age group.     

Nummular headache: a prospective series of 14 new cases

OBJECTIVE: To study the clinical features of nummular headache (NH) and get an approach to its epidemiology. BACKGROUND: NH has been recently described as a primary disorder characterized by head pain exclusively felt in a small rounded area typically 2-6 cm in diameter. METHODS: Through a 1-year period we have studied all patients referred to our neurologic clinic because of head pain exclusively felt in a small-circumscribed area, and not attributed to another disorder. All the patients had normal neurological, analytical, and neuroimaging examinations. All the patients belonged within the same regional care system comprising 220,000 inhabitants. RESULTS: A total of 11 females and 3 males were studied. Based in our hospital series, the incidence was 6.4/100,000/year. The mean age at the onset was 38 years (range: 13-72). Only three patients had another concurrent headache: migraine (n = 2), and trigeminal neuralgia (n = 1) which proved to have an independent course. All the patients reported head pain exclusively felt in either a rounded (n = 12) of 1-6 cm diameter, or an oval area (n = 2) of 5 x 3 cm, and 2 x 3 cm, respectively. Both size and shape of the painful area remained constant since the onset of symptoms. The location of the symptomatic area was mostly parietal (n = 7) or temporal (n = 5), but also frontal (n = 1) and in occiput (n = 1). The background pain was mostly mild-to-moderate, but also moderate-to-severe pain was reported. Exacerbations-either spontaneous or precipitated by combing hair or touching the symptomatic area-were reported by 8 patients. The temporal pattern was chronic-continuous (n = 7) and episodic (n = 7). Ten patients reported a variable combination of sensory disturbance (tenderness, hypoesthesia, hyperalgesia, and allodynia) in the symptomatic area. There were no autonomic accompaniments. Treatment was generally not necessary. When needed, standard oral doses of paracetamol usually sufficed. CONCLUSIONS: NH emerges as a clear-cut clinical picture. It is a noninfrequent primary headache. The particular topography suggests the pain has a probable epicranial source conveyed by, or originated in, one/a few terminal branch(es) of the cutaneous nerves of the scalp.     

Topical butyrate improves efficacy of 5-ASA in refractory distal ulcerative colitis: results of a multicentre trial

BACKGROUND: The treatment of distal ulcerative colitis, refractory to conventional 5-ASA/steroid treatment, is still a matter of debate. The present study aimed at confirming, with adequate statistical power, previous data indicating the usefulness of topical butyrate and 5-ASA in the treatment of this condition. DESIGN: Double-blind, placebo-controlled, multicentre study. A total of 51 patients with distal (< 65 cm) ulcerative colitis, refractory to topical 5-ASA/cortisone, were randomly allocated to receive topical 5-ASA 2 g and 80 mM L-1 sodium-butyrate bid (Group A; 24 patients) or 5-ASA 2 g and 80 mL saline bid (Group B; 27 patients) for 6 weeks. Sigmoidoscopy with biopsies, as well as clinical and laboratory evaluations, were carried out at enrollment and at the end of the trial. Primary endpoints: remission or marked improvement in endoscopic, histologic and clinical findings. RESULTS: Most parameters showed a significant improvement vs. baseline in both groups. Remission in six patients and improvement in 12 patients in Group A vs. one remission and 13 with improvement in Group B (P < 0.05). A significant difference in favour of Group A was recorded regarding the number of bowel movements (P < 0.01), urgency (P < 0.05) and the patients' self evaluation (P < 0.01). DISCUSSION: The combined treatment with topical butyrate and 5-ASA is significantly more effective than 5-ASA alone in the management of refractory distal colitis. Further improvements in the treatment of refractory distal ulcerative colitis may be feasible based on the identification of patient subgroups and the association of two or more active drugs. Butyrate may well be one of them.     

Duration of attacks of first division trigeminal neuralgia

Objective measurements of duration of attacks have been performed in 8 (5 female and 3 male) patients suffering from primary first division (V-1) trigeminal neuralgia. The mean age of the patients was 67.5 +/- 11.4 years, and the mean age at onset 64.0 +/- 9.7 years. During the study the patients were off treatment. A total of 192 attacks were witnessed by the authors and exactly timed by a stop-watch. The duration of attacks ranged from 2 to 32 s, with a mean of 6.5 +/- 6.1 s. The unweighted mean was 8.8 +/- 5.7 s, with a range of 2.4-17.5 s. With the present data the duration of attacks of V-1 neuralgia has been exactly determined, and the clinical distinction of V-1 neuralgia from other shortlasting headaches, particularly from SUNCT, has been substantially clarified.     

Coenzyme Q10 deficiency and response to supplementation in pediatric and adolescent migraine

BACKGROUND: Coenzyme Q10 (CoQ10) has been suggested to be effective in the prevention of migraine, and levels can be quantified with standardized reference ranges. OBJECTIVE: This study documents the prevalence of CoQ10 deficiency in migraine headache and examines the potential effectiveness of supplementation. METHODS: We assessed patients attending a tertiary care center with frequent headaches for CoQ10 deficiency. We recommended patients with low CoQ10 levels begin supplementation with CoQ10 as part of their multidisciplinary treatment plan. We assessed response to treatment including correction of CoQ10 deficiency, overall headache improvement, and headache disability. RESULTS: CoQ10 was measured in 1550 patients (mean age 13.3 +/- 3.5, range 3 to 22 years). The mean total CoQ10 level was 0.60 +/- 0.20 microg/mL (range 0.21 to 1.77 microg/mL). Of these patients, 32.9% were below the reference range. Patients with low CoQ10 were recommended to start 1 to 3 mg/kg per day of CoQ10 in liquid gel capsule formulation. In a subset of patients who returned for timely follow-up (mean, 97 days), the total CoQ10 level improved to 1.20 +/- 0.59 microg/mL (P < .0001), while the headache frequency improved from 19.2 +/- 10.0 to 12.5 +/- 10.8 (P < .001) and headache disability assessed with PedMIDAS improved from 47.4 +/- 50.6 to 22.8 +/- 30.6 (P < .001). CONCLUSIONS: Deficiency of CoQ10 may be common in pediatric and adolescent migraine. Determination of deficiency and consequent supplementation may result in clinical improvement. Further analysis involving more scientifically rigorous methodology will be required to confirm this observation.     

Chronic Paroxysmal Hemicrania and Hemicrania Continua. Interval Between Indomethacin Administration and Response

The interval between indomethacin dosage and clinical response was assessed in hemicrania continua (n=12) and chronic paroxysmal hemicrania (n=11) sufferers. The number of trials per patient ranged from I to 30. At the time of testing, the patients had "considerable" pain after discontinuation of the drug. The dosage used was the usual one for that patient at the given pain level; ie, 25 or 50 mg tid. All the patients had a complete, long-term response to treatment. Nevertheless, the average interval between drug intake and pain relief during the present study ranged beween 30 minutes and 48 hours in both disorders. In most patients (10 in both groups), the indomethacin effect was complete within 24 hours, and frequently within 8 hours. It is suggested that interindividual differences in dosage and timing to abolish the headaches may be due to different bioavailability or individual sensitivity. Recommendations on indomethacin testing in unilateral headaches are given.     

穴位热痛刺激治疗无先兆偏头痛的近期镇痛疗效观察

目的 观察穴位热痛刺激治疗无先兆偏头痛患者的近期镇痛疗效。 方法 采用随机数字表法将120例无先兆偏头痛患者分为观察组及对照组，每组60例。对照组患者给予西比灵口服，每晚1次，每次5 mg，治疗4周为1个疗程。观察组患者在对照组干预基础上辅以穴位热痛刺激，取穴风池、率谷、阳陵泉、外关、太阳、印堂，选用Pathway疼痛及感觉评估系统配置的圆形刺激器，当刺激器加热至54.5 ℃时发放可调节脉冲热刺激，单个脉冲热刺激其脉宽为0.3 s，刺激间隔10 s，每个穴位连续刺激5次后换下一穴位，各穴位循环交替刺激，共治疗20 min，每日治疗1次，治疗4周为1个疗程。记录治疗前、后2组患者头痛发作频率、持续时间、疼痛视觉模拟评分(VAS)、头痛伴随症状评分、偏头痛特异生活质量问卷量表（MSQ）评分，并对比2组患者近期疗效差异。 结果 治疗后观察组患者头痛发作频率［（1.27±0.13）次/月］、头痛持续时间［（2.51±0.22）分钟/次］、疼痛VAS评分［（0.43±0.08）分］、头痛伴随症状评分［（0.21±0.20）分］、MSQ功能受限评分［（79.0±10.2）分］、功能障碍评分［（82.6±10.3）分］及情感评分［（85.2±10.5）分］均较治疗前及对照组明显改善（均P<0.05）；另外治疗后观察组患者总有效率（95.0%）亦显著优于对照组水平（80.0%），组间差异具有统计学意义（P<0.05）。所有患者在治疗期间其心率、血压均未出现不良反应，热痛刺激部位无感染、红肿等异常表现。 结论 穴位热痛刺激治疗无先兆偏头痛患者近期疗效显著，并且治疗过程安全可靠、副反应少，为偏头痛患者提供了一种新的治疗方法，值得临床推广、应用。     

Eletriptan for the acute treatment of migraine in adolescents: results of a double-blind, placebo-controlled trial

BACKGROUND: Eletriptan is a potent 5-HT(1B/1D) agonist with proven efficacy in the acute treatment of migraine in adults. OBJECTIVE: To evaluate the efficacy and tolerability of eletriptan 40 mg versus placebo in adolescent patients (aged 12-17). METHODS: A multicenter, double-blind, parallel-group, placebo-controlled trial was conducted comparing 40 mg of oral eletriptan with placebo for the treatment of migraine in adolescent patients. The primary efficacy endpoint was 2-hour headache response, and a number of secondary endpoints were also evaluated. An exploratory analysis evaluated which clinical and demographic characteristics might be correlated with high placebo response. RESULTS: Of 274 patients who treated a migraine attack, 267 were evaluated for efficacy (n = 138 eletriptan; n = 129 placebo) at 2 hours post-dose. There was no significant difference in 2-hour headache response for eletriptan 40 mg versus placebo (57% vs 57%), and no significant improvements were observed for any of the outcomes at 1 or 2 hours post-dose. By contrast, there was a significant advantage for eletriptan 40 mg in reducing headache recurrence within 24 hours post-dose (11% vs 25%, P= .028), and post hoc analyses showed statistically significant differences for sustained headache response rates (52% vs 39%; P= .04) and sustained pain-free response rates (22% vs 10%; P= .013). The strongest clinical predictor of placebo response was triptan-na?ve status (i.e., no previous use of any triptan). Eletriptan 40 mg was well tolerated in this population, and the profile of adverse events was similar to that observed in Phase III trials in adult patients. CONCLUSIONS: The high placebo response rates reported here for 1- and 2-hour outcomes are in accordance with other studies of triptans in adolescent patients. The evaluation of treatment effect in adolescent migraine might benefit from use of more stringent outcome measures, such as headache recurrence, sustained headache response, and sustained pain-free response at 24 hours post-dose.     

Headache and hemodialysis: a prospective study

OBJECTIVE: To determine the prevalence and clinical characteristics of headache in patients undergoing hemodialysis and to compare the prevalence of headache prior to and following the beginning of a hemodialysis program. BACKGROUND: About 70% of patients receiving hemodialysis complain of headache. Despite this, headaches have not been well studied in this group of patients. METHODS: We evaluated a series of patients with chronic renal failure who attended 3 hemodialysis services in a Brazilian town from January of 1998 to December of 1999. Patients with headache were prospectively followed and classified according to the International Headache Society criteria. The headaches were also categorized according to their temporal profile relative to hemodialysis. RESULTS: Headache was reported by 87 (70.7%) of the 123 patients studied. Prior to beginning dialysis, 48% had migraine, 19% had episodic tension-type headache, and 8% had both. Headache related to arterial hypertension was the second most frequent headache diagnosis in these patients (25.4%). Fifty patients (57.5%) experienced headache during the session of hemodialysis. Thirty-four were classified as dialysis headache, 7 were classified as migraine, 7 as episodic tension-type headache, and 2 were unclassified. Twenty-four patients (27.6%) reported dramatic improvement of their headaches after the beginning of the dialysis program. CONCLUSIONS: Headache is common in patients undergoing hemodialysis. Classification of such headaches according to the International Headache society criteria may be difficult.     

Divalproex in the long-term treatment of chronic daily headache

OBJECTIVE: The purpose of this study was to assess the safety and efficacy of divalproex sodium in the long-term treatment of chronic daily headache. Correlations between treatment variables were assessed. BACKGROUND: Controlled and open-label trials of divalproex sodium have previously demonstrated its efficacy and safety in the treatment of migraine and chronic daily headaches. These data were primarily short-term and did not examine interaction between treatment variables. METHODS: Retrospective chart review with data extraction was conducted from headache diaries of 642 current patients under treatment with divalproex sodium for chronic daily headaches. One hundred thirty-eight of the patients were treated with only divalproex sodium. Demographic variables including age, sex, initial and final body weights, adverse events, dose of divalproex sodium, duration of treatment, and the ability to differentiate their chronic daily headache into its migraine and tension-type headache components were analyzed. Baseline and end of study headache frequency indices were obtained. RESULTS: The mean improvement was 47%, with an improvement in migraine of about 65%. At least a 50% reduction in headache frequency was reported by 93 of the 138 patients receiving treatment with only divalproex sodium. No correlation between response and age, sex, duration of treatment, and the prescribed dose of divalproex sodium was demonstrated. Adverse events occurred in approximately 35% of the patients. None were severe. Women were more likely to experience adverse effects than men. Weight gain, however, occurred less commonly in women (mean, 1.9 lbs) than in men (mean, 7 lbs). Initial body weight and age did not correlate with the weight change. CONCLUSIONS: Divalproex sodium can be used for a prolonged period as a sole agent for the successful treatment of chronic daily headache. Nearly 75% of the patients had at least a 50% reduction in headache frequency, and adverse effects occurred in approximately one third. Weight gain was negligible and hepatotoxicity did not occur during treatment periods of up to 6 years.     

Prophylactic treatment of migraine in children. Part 2. A systematic review of pharmacological trials

The aim of this study was to assess the efficacy of pharmacological prophylactic treatments of migraine in children. Databases were searched from inception to June 2004 and references were checked. We selected controlled trials on the effects of pharmacological prophylactic treatments in children with migraine. We assessed trial quality using the Delphi list and extracted data. Analyses were carried out according to type of intervention. A total of 20 trials were included. Headache improvement was significantly higher for flunarizine compared with placebo (relative risk 4.00, 95% confidence interval 1.60, 9.97). There is conflicting evidence for the use of propranolol. Nimodipine, clonidine, L-5HTP, trazodone and papaverine showed no effect when compared with placebo. All medications were well tolerated and adverse events showed no significant differences. Flunarizine may be effective as prophylactic treatment for migraine in children. Because of the small number of studies and the methodological shortcomings, conclusions regarding effectiveness have to be drawn with caution.     

Intranasal Lidocaine for the Treatment of Migraine Headache: A Randomized, Controlled Trial

OBJECTIVE: To evaluate the effect of intranasal lidocaine for immediate relief (5 minutes) of migraine headache pain. METHODS: A randomized, double-blind, placebo-controlled clinical trial at two university-affiliated community teaching hospitals enrolled patients 18-50 years old with migraine headache as defined by the International Headache Society. Patients who were pregnant, lactating, known to abuse alcohol or drugs, or allergic to one of the study drugs, those who used analgesics within two hours, or those with a first headache were excluded. Statistical significance was assessed by using chi-square or Fisher's exact test for categorical variables and Student's t-test for continuous variables. Patients rated their pain on a 10-centimeter visual analog scale (VAS) prior to drug administration and at 5, 10, 15, 20, and 30 minutes after the initial dose. Medication was either 1 mL of 4% lidocaine or normal saline (placebo) intranasally in split doses 2 minutes apart and intravenous prochlorperazine. Medications were packaged so physicians and patients were unaware of the contents. Successful pain relief was achieved if there was a 50% reduction in pain score or a score below 2.5 cm on the VAS. RESULTS: Twenty-seven patients received lidocaine and 22 placebo. No significant difference was observed between groups in initial pain scores, 8.4 (95% CI = 7.8 to 9.0) lidocaine and 8.6 (95% CI = 8.0 to 9.2) placebo (p = 0.75). Two of 27 patients (7.4%, 95% CI = 0.8, 24.3) in the lidocaine group and three of 22 patients (13.6%, 95% CI = 2.8 to 34.9) in the placebo group had immediate successful pain relief (p = 0.47), with average pain scores of 6.9 (95% CI = 5.9 to 7.8) and 7.0 (95% CI = 5.8 to 8.2), respectively. No difference in pain relief was detected at subsequent measurements. CONCLUSION: There was no evidence that intranasal lidocaine provided rapid relief for migraine headache pain in the emergency department setting.     

A Pooled Analysis of the Safety and Efficacy of Iclaprim Versus Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections in Patients With Intravenous Drug Use: Phase 3 REVIVE Studies

PurposeThis analysis evaluates the efficacy and safety of iclaprim versus vancomycin for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in patients who were intravenous drug users (IVDUs).MethodsA total of 621 patients who were IVDUs from 2 parallel Phase III, double-blind, randomized (1:1), active-controlled, multinational, multicenter trials (REVIVE-1 and REVIVE-2) were analyzed separately and pooled. This post hoc analysis summarizes the efficacy and safety profile of iclaprim 80 mg fixed dose compared with vancomycin 15 mg/kg administered intravenously during 2 h every 12 h for 5–14 days among this population. The primary end point of these studies was to determine whether iclaprim was noninferior (10% margin) to vancomycin in achieving a ≥20% reduction in lesion size at 48–72 h after initiation of treatment with the study drug (early clinical response) in the intent-to-treat population. The safety profile was assessed based on adverse events and laboratory parameters.FindingsIclaprim had higher early clinical response rates (85.8%; 95% CI, 81.5%–89.4%) compared with vancomycin (79.8%; 95% CI, 74.8%–84.2%) among patients with ABSSSIs who were IVDUs, with a treatment difference of +6.00% (95% CI, 0.06–12.0). The safety profile was similar in the iclaprim and vancomycin arms, with 3.7% and 5.0%, respectively, of patients discontinuing study therapy because of adverse events and 1.9% and 3.4%, respectively, of patients developing serious adverse events.ImplicationsIclaprim had a higher early clinical response rate and favorable safety profile compared with vancomycin for the treatment of ABSSSIs in patients who were IVDUs. Iclaprim may be a valuable treatment option for ABSSSIs in this patient population.     

Subcutaneous Sumatriptan in the Clinical Setting: The First 50 Consecutive Patients With Acute Migraine in a Pediatric Neurology Office Practice

An open prospective study was undertaken to assess the efficacy and safety of subcutaneous sumatriptan in 50 consecutive children ages 6 to 18 years with severe migraine. There were 28 females and 22 males. The dose of sumatriptan was 0.06 mg/kg. Parameters included overall efficacy, time to relief, recurrence rate, adverse events, and objective global rating. Overall efficacy, defined by headache reduction from severe or moderate to mild or none, was 78%. Twenty-six percent responded within 30 minutes, 46% responded in 60 minutes, and 6% responded between I to 2 hours. Twenty-two percent had no response or a suboptimal response. Recurrence rate was only 6%. There was a difference in efficacy between male and female, as 91% of the males responded, while only 68% of the females responded. The males had more migraine alone while the females had migraine often with a coexistent tension-type headache. Eighty percent of all the patients had some adverse event which was usually mild and transient; however, one patient developed a transitory confusional state which resolved in 2 hours. Eighty-four percent reported a global rating of good to excellent, while 16% rated the treatment only fair to poor. These findings suggest that subcutaneous sumatriptan can be both effective and safe in childhood migraine, especially in dealing with migraine alone,     

L-745,870 reduces L-DOPA-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease

L-DOPA-induced dyskinesia remains an unmet challenge in the treatment of Parkinson's disease (PD). Here, we investigate the potential antidyskinetic efficacy of 3-([4-(4-chlorophenyl)piperazin-1-yl]methyl)-1H-pyrrolo[2,3-b]pyridine (L-745,870), a potent and selective dopamine D(4) receptor antagonist with a good toxicology profile and an excellent safety and tolerability record in phase I/II clinical studies, for non-PD indications. Six macaques were rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. After induction of stable and marked dyskinesia, animals were administered acute challenges of L-745,870 in combination with L-DOPA. To guarantee D(4) selectivity at the doses used in the study, we determined the plasma, cerebrospinal fluid, and brain levels of L-745,870. Coadministration of L-745,870 (1 mg/kg) and L-DOPA significantly reduced the severity of dyskinesia, by up to 59%, in comparison with L-DOPA alone (P < 0.01). L-745,870 had no effect on the duration of antiparkinsonian benefit (ON-time) (P > 0.05). However, L-745,870 (1 mg/kg) significantly increased the duration of ON-time without disabling dyskinesia (+204%; P < 0.001) and decreased duration of ON-time with disabling dyskinesia compared with L-DOPA alone (-56%; P < 0.01). Brain levels of L-745,870 (～600 ng/g) were within the range at which L-745,870 provides selective D(4) receptor antagonism. Plasma levels were comparable with those demonstrated to be well tolerated in human studies. These data suggest that selective D(4) receptor antagonists represent a potential therapeutic approach for L-DOPA-induced dyskinesia. It is noteworthy that L-745,870 has already undergone significant clinical development, has an excellent profile for a therapeutic candidate, and could be advanced rapidly to phase IIa clinical studies for dyskinesia in PD.     

SUNCT syndrome responsive to lamotrigine

BACKGROUND: Short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection, tearing, rhinorrhea (SUNCT syndrome) is a headache form generally refractory to drug therapy. Occasional patients with SUNCT have been reported with a successful response to lamotrigine. OBJECTIVE: To report two patients with SUNCT treated with lamotrigine. METHODS: Clinical history, neurologic examination, and brain magnetic resonance imaging. RESULTS: Both patients with SUNCT syndrome were successfully treated with lamotrigine. In both cases, when lamotrigine was tapered off, the attacks reappeared, only to disappear when the dose was again increased. In addition, lamotrigine was well tolerated and no undesired side-effects were reported. CONCLUSION: If the positive effect of lamotrigine in patients with SUNCT is confirmed in other cases, lamotrigine could become the first specific treatment for SUNCT syndrome.