Placebo-controlled pilot trial of mecamylamine for treatment of autism spectrum disorders.

OBJECTIVE: To explore possible benefits of a nicotinic acetylcholine receptor (nAChR) agent for autistic symptoms based on postmortem observation of nAChR abnormalities (deficient α4ß2 nAChRs, excess α7 nAChRs) in brains of patients with autism. METHOD: Mecamylamine, because of its safety record in children with other disorders, was chosen for this first exploration. Twenty children with autism spectrum disorder age 4-12 years were randomly assigned for 14 weeks to placebo (n=8) or mecamylamine (n=12) in ascending fixed doses: 0.5 mg/day for 6 weeks, 2.5 mg for 2 weeks, then 5 mg/day for 6 weeks. Improvement was rated by a blinded independent evaluator. Because of small sample, data analysis was descriptive. RESULTS: Eighteen participants (10 mecamylamine, 8 placebo) completed the study. All doses were well tolerated; the only side effect of note was constipation (50% compared with 25% of placebo group). Three children had clinically nonsignificant electrocardiographic QT prolongation. Both groups showed modest to moderate improvement, but differences between groups were negligible. On the primary outcome measure, the Ohio Autism Clinical Impressions Scale, 90% of the active treatment group showed improvement at some point (but only 40% sustained it), compared with 62% on placebo. Of the four in active treatment that sustained improvement, three had a maximum dose of 0.13-0.15 mg/kg/day, while those who regressed had doses ≥0.18 mg/kg/day. Graphed means suggested better outcome with lower mg/kg and longer medication duration. Four parents spontaneously reported reduced hyperactivity and irritability and better verbalization and continued mecamylamine at their own expense. CONCLUSION: Mecamylamine appeared to be safe, but not very effective in autism. The suggestion of better results at lower doses and longer exposure warrants consideration for future trials. The next step would be exploration of a more specific α4ß2 nAChR agonist, such as varenicline.

[Superior cervical ganglion: an anatomical variant. Are variations of the cranial carotid artery a risk factor for accidental intravascular injection?]. / Ganglion cervicale superius: eine anatomische Besonderheit. Variationen der A. carotis interna als Risiko einer akzidentellen intravasalen Injektion?

A variation of the cranial carotid artery is demonstrated in an anatomical specimen revealing possible complications of ganglionic local opioid analgesia at the superior cervical ganglion. Located in the area of the puncture site, a loop of the aberrant carotid artery adheres closely to the pharyngeal wall in the medial position, shortening the distance between the arterial lumen and the oral cavity to 5 mm. With an incidence of 25%, an aberrant carotid artery could possibly facilitate an accidental intravascular injection during ganglionic local opioid application at the superior cervical ganglion.

Effects of trimetaphan-induced deliberate hypotension on human cochlear blood flow.

In order to observe the reaction of cochlear blood flow (CBF) to trimetaphan (TMP)-induced hypotension, CBF was measured with laser-Doppler flowmetry in 7 human subjects during general anaesthesia for middle ear surgery. All subjects showed a decrease in mean arterial pressure (MAP) during intravenous infusion of TMP, followed by a gradual return to the baseline level after termination of the infusion. The CBF generally followed the MAP changes with the same pattern. Three of the seven subjects demonstrated a CBF change larger than the maximum MAP change, indicating the lack of a local autoregulatory mechanism in CBF. On the other hand, CBF changes were smaller in magnitude than the maximum change in MAP for the rest of the subjects, suggesting an autoregulatory mechanism in CBF. However, since the audiograms from these subjects indicated profound damage along the cochlear basal turn probably due to middle ear inflammation, concomitant vascular damage in this region offers another possible explanation for the inappropriate CBF changes. The present observations may also suggest that deliberately TMP-induced hypotension has a potentially harmful effect on CBF during otological surgery that attempts to preserve or improve hearing.

The use of topical 4% lidocaine in spheno-palatine ganglion blocks for the treatment of chronic muscle pain syndromes: a randomized, controlled trial.

To assess the efficacy of 4% topical lidocaine in spheno-palatine blocks, a randomized controlled trial was carried out on patients with chronic muscle pain syndromes. Sixty-one patients (42 with fibromyalgia (FM) and 19 with myofascial pain syndrome (MPS)) completed the trial. Outcome measures included pain intensity, a daily pain diary, headache frequency, sensitivity to pressure using a dolorimeter, anxiety, depression, and sleep quality. Patients were randomized to receive either 4% lidocaine or sterile water (placebo) 6 times over a 3-week period. Both subjects and investigators were blind to treatment allocation. The results showed that 4% lidocaine had no superiority over placebo in any of the outcome measures. Twenty-one subjects (35%) showed a decrease in pain which was greater than 30% of their baseline value. Of these 21 subjects, 10 received lidocaine and 11 received placebo. These data suggest that, in this population, 4% lidocaine is no better than placebo in the treatment of chronic muscle pain.

Ultrasound imaging for stellate ganglion block: direct visualization of puncture site and local anesthetic spread. A pilot study.

BACKGROUND AND OBJECTIVES: Stellate ganglion block (SGB) inhibits sympathetic innervation and is a common treatment for reflex sympathetic dystrophy. During the positioning of the needle, there is a risk of injury to the adjacent structures. The aim of the study was to develop an ultrasonographic imaging technique for the performance of SGB. METHODS: Twelve patients (ASA I-II) underwent SGB first by using the blind standard technique (group A: 8 mL bupivacaine 0.25%) and a second time by using an ultrasonographic imaging technique (group B: 5 mL bupivacaine 0.25%). In group B a 10 MHz ultrasound scanning probe was used to identify the anatomic structures and to guide the needle toward the transverse process of C6. RESULTS: Stellate ganglion block was satisfactory in 11 of 12 attempts by the blind technique. Ultrasonographic guidance (group B) resulted in a complete block in all patients. Onset of block was observed within 10 minutes in only 10 of 12 group A patients, while all patients in group B exhibited an adequate block after 10 minutes. During the imaging technique, the needle was inserted to an average depth of 22 +/- 3 mm and the injection of 5 mL bupivacaine resulted in an anesthetic depot with a mean diameter of 14 +/- 3 mm. Distance from the depot to the vagal nerve was 5 +/- 3 mm and 5 +/- 4 mm to the root of C6. All patients (n = 4) with a distance of < 1 mm between anesthetic depot and the root of C6 developed paresthesia within the corresponding cutaneous segment. Blind technique resulted in hematoma formation in three study patients, with no hematoma occurring during imaging technique. CONCLUSIONS: Ultrasonographic guided SGB may improve safety and allows the visualization of the local anesthetic depot. Studying the local anesthetic spread might allow the avoidance of side effects as well as typical complications of SGB.