The Bidirectional Movement of the Frontalis Muscle: Introducing the Line of Convergence and Its Potential Clinical Relevance.

BACKGROUND: Cosmetic treatment of the forehead using neuromodulators is challenging. To avoid adverse events, the underlying anatomy has to be understood and thoughtfully targeted. Clinical observations indicate that eyebrow ptosis can be avoided if neuromodulators are injected in the upper forehead, despite the frontalis muscle being the primary elevator. METHODS: Twenty-seven healthy volunteers (11 men and 16 women) with a mean age of 37.5 ± 13.7 years (range, 22 to 73 years) and of diverse ethnicity (14 Caucasians, four African Americans, three Asians, and six of Middle Eastern descent) were enrolled. Skin displacement vector analyses were conducted on maximal frontalis muscle contraction to calculate magnitude and direction of forehead skin movement. RESULTS: In 100 percent of investigated volunteers, a bidirectional movement of the forehead skin was observed: the skin of the lower forehead moved cranially, whereas the skin of the upper forehead moved caudally. Both movements converged at a horizontal forehead line termed the line of convergence, or C-line. The position of the C-line relative to the total height of the forehead was 60.9 ± 10.2 percent in men and 60.6 ± 9.6 percent in women (p = 0.941). Independent of sex, the C-line was located at the second horizontal forehead line when counting from superior to inferior (men, n = 2; women, n = 2). No difference across ethnicities was detected. CONCLUSIONS: The identification of the C-line may potentially guide practitioners toward more predictable outcomes for forehead neuromodulator injections. Injections above the C-line could mitigate the risk of neuromodulator-induced brow ptosis.

Preventing, identifying, and managing cosmetic procedure complications, part 1: soft-tissue augmentation and botulinum toxin injections.

This column highlights some of the potential complications that have been associated with cosmetic procedures. Tips for how dermatology residents may prevent, identify, and manage complications from cosmetic procedures for optimal patient outcomes is provided. In part 1 of this series, soft-tissue augmentation and botulinum toxin injections are discussed. Part 2 will focus on chemical peels and laser therapy.

Influence of upper and temporal transconjunctival sclerocorneal incision on marginal reflex distance after cataract surgery.

BACKGROUND: Ptosis incidence following cataract surgery is reduced with a recently developed phacoemulsification technique using a small incision. However, it remains uncertain whether an upper transconjunctival sclerocorneal incision can cause minor blepharoptosis. In the present prospective study, patients underwent cataract surgery with either an upper or temporal 2.4-mm transconjunctival sclerocorneal incision. We measured the marginal reflex distance 1 (MRD1) preoperatively and postoperatively, and compared these measurements between the two different incision types. Further we explored the risk factors of the postoperative MRD1 reduction. METHODS: The study population included patients who underwent cataract surgery on both eyes at Aichi Medical University between October 2013 and September 2015. In each patient, one eye was operated using an upper 2.4-mm transconjunctival sclerocorneal incision, and the other with a temporal incision. We prespecified that an MRD1 difference of ≥0.5 mm between the pre- and post-surgical measurements indicated postoperative ptosis, which was a strict criterion. MRD1 was measured using digital photography, and we calculated the difference between the preoperative and postoperative MRD1 values. This change in MRD1 was compared between the groups with different incision locations. The change in MRD1 was analyzed by using the multivariate regression model including incision position (temporal or upper), preoperative MRD1, and preoperative distance between medial and lateral canthi. RESULTS: We assessed data from a total of 34 patients. The mean change in MRD1 from pre-operation to post-operation measurements was -0.26 ± 0.93 with the temporal incision and -0.24 ± 0.86 with the upper incision. The mean difference in the change in MRD1 between the different two incision types was -0.02, with a 95 % CI of -0.24 to 0.20, establishing equivalence between these incision types. The multivariate regression analysis showed that the preoperative MRD1 was significantly associated with the reduction of MRD1 after surgery (p = 0.034). CONCLUSIONS: Cataract surgery using upper and temporal 2.4-mm transconjunctival sclerocorneal incisions are clinically equivalent with regards to change in MRD1, and neither incision type caused critical postoperative ptosis. The longer preoperative MRD1 was significantly associated with the reduction of MRD1 after surgery. TRIAL REGISTRATION: Current Controlled Trials UMIN000022310 . Retrospectively registered 14 May 2016.

Temporalis Muscle Transfer for the Treatment of Lagophthalmos in Patients With Leprosy: Refinement in Surgical Techniques to Prevent Postoperative Ptosis.

Facial paralysis resulting from leprosy has a serious impact on the entire face especially in the areas innervated by the facial nerves. In particular, lagophthalmos in patients with leprosy causes exposure keratitis, corneal, and conjunctival dryness, which can progress to blindness and disfigurement. Recently, we conducted 4 different temporalis muscle transfer (TMT) methods over the last 4 years to reduce ptosis. The methods used included Brown-McDowell, McCord-Codner, modified Gillies-Anderson, and modified Gillies. Seventy-five TMT operations in 60 patients were performed between 2011 and 2014. The mean age was 70.1. Fifteen patients had bilateral TMT procedures. As a result, ptosis appeared in 14(18.7%) of 75 TMT procedures for 4 years. To prevent or correct this complication, the following 4 technical refinements have simplified the surgery and yield better surgical outcomes. First, an increase in the length of the temporalis muscle flap to approximately 8 cm with a parallel course to the lateral canthus will reduce oblique pull. Second, the width of the fascia sling in the upper eyelid is narrowed (3-4 mm) to reduce weight on the eyelid. Third, the fascia sling in the upper lid should not be located along the full length of the upper lid but terminate 3.5 cm medial to lateral canthal tendon and in other words, should not be tied at the medial canthal tendon to reduce tension and weight. Lastly, the fascia sling in the eyelid should be located shallow (probably in subdermal layer) and as near as possible to the lid margin to prevent any functional disturbance in levator aponeurosis.

Mechanical testing of lid speculae and relationship to postoperative ptosis.

AIMS: Postoperative lid malpositions are known complications of routine intraocular surgery and were previously attributed to the use of a bridle suture or the myotoxic effect of retrobulbar or peribulbar anaesthetics. However, lid malpositions are still seen under topical anaesthesia. Recent studies have implicated the lid speculum as a factor. Patients with narrower vertical palpebral apertures have been shown to develop postoperative ptosis more frequently, but the reason is unknown. This is the first study to determine the forces exerted by lid speculae over a range of palpebral apertures. METHODS: Mechanical testing was undertaken using a Bose 3200 materials testing machine. Tests were undertaken on four disposable and four reusable speculae. The force used to compress each speculum was compared over a range of displacements. A two-sample t-test was used to compare the stiffness of the two types of speculum. RESULTS: The stiffness of the reusable speculum was significantly greater than the disposable speculum (P=0.002). The stiffness of each speculum was greatest at the range of displacement corresponding to the narrower palpebral apertures. CONCLUSIONS: Different speculae exert significantly different forces on patients' eyelids during surgery. The patients who experience the greatest compression from the speculae are those with the smallest palpebral apertures. This may explain why these patients are more likely to develop postoperative lid malpositions.

Dysport (botulinum toxin type A) in routine therapeutic usage: a telephone needs assessment survey of European physicians to evaluate current awareness and adherence to product labeling changes.

BACKGROUND: Botulinum neurotoxin type A is a well-established treatment for a number of conditions involving muscle hyperactivity. Dysport (Ipsen Ltd, Wrexham, United Kingdom) is a botulinum neurotoxin type A preparation that has been available for a number of therapeutic uses for over 20 years in the European Union (EU). This survey was part of the EU botulinum toxin risk management plan to identify potential educational needs of injectors by collecting data on their routine practice administration of Dysport and their awareness of potential adverse events (AEs) that are included in the current product labeling. METHODS: Dysport-experienced injectors in 5 EU countries were surveyed via telephone about their experience of Dysport in patients with cervical dystonia, adult upper and lower limb spasticity, pediatric cerebral palsy, and blepharospasm/hemifacial spasm. RESULTS: The reconstitution dilution volume most often used was 2.5 mL per 500 U for all indications. The mean total dose ranged from 387 to 530 U for cervical dystonia, 508 to 773 U for upper limb spasticity, 600 to 832 U for lower limb spasticity, 375 to 700 U for pediatric cerebral palsy, and 54 to 213 U for blepharospasm/hemifacial spasm. The potential AEs most commonly mentioned by surveyed physicians were dysphagia for cervical dystonia, arm muscle weakness for upper limb spasticity, leg muscle weakness for lower limb spasticity, and pediatric cerebral palsy and ptosis for blepharospasm/hemifacial spasm. CONCLUSIONS: The results indicate that product-labeling recommendations are generally applied in clinical practice and that there is a good familiarity with potential AEs based on clinical condition. Nevertheless, the survey shows that experienced injectors do sometimes deviate from the manufacturers labeling recommendations, highlighting the importance of ongoing education.

[Prevention and management of locoregional complications of botulinum A toxin injections in cosmetic treatment]. / Prévention et gestion des complications locorégionales des injections de toxine botulique A en esthétique.

Botulinum toxin serotype A injections used in treating dynamic wrinkles is one of the least invasive cosmetic procedures. High patient satisfaction and low onset of always moderate side effects contribute to the growing popularity of botulinum toxin injections in cosmetic treatment over the past few years. Years of experience and use, in therapeutics [1,2] and esthetics (20 years) have proven the efficacy and the safety of this wrinkle treatment. Today, no severe or long-term side effects have been reported in esthetics. This article discusses only the most frequent locoregional effects. They are rare, moderate, transitory, and totally reversible. Properly informing and selecting patients will contribute to successfully preventing and managing these effects.

Antidepressant activity of some Hypericum reflexum L. fil. extracts in the forced swimming test in mice.

We previously reported that oral administration of the methanol extract obtained from the aerial part in blossom of Hypericum reflexum L. fil. was active in the tetrabenazine and forced swimming test. In the present study, the effect of the aqueous, butanol and chloroform fractions obtained from the methanol extract of this species on the central nervous system was investigated in mice, particularly in animal models of depression. Antidepressant activity was detected in the butanol and chloroform fractions of this species using the forced swimming test since both fractions induced a significant reduction of the immobility time, producing no effects or only a slight depression on spontaneous motor activity when assessed in a photocell activity meter. Moreover, these fractions did not alter significantly the pentobarbital-induced sleeping time. On the other hand, the chloroform fraction produced a slight but significant hypothermia and was also effective in antagonizing the ptosis induced by tetrabenazine. Furthermore, the butanol fraction produced a slight potentiation of the head twitches and syndrome induced by 5-HTP. Taken together, these data indicate that the butanol and chloroform fractions from Hypericum reflexum possess antidepressant-like effects in mice, providing further support for the traditional use of these plants in the Canary Islands folk medicine against central nervous disorders.

Ptosis: causes, presentation, and management.

Drooping of the upper eyelid (upper eyelid ptosis) may be minimal (1-2 mm), moderate (3-4 mm), or severe (>4 mm), covering the pupil entirely. Ptosis can affect one or both eyes. Ptosis can be present at birth (congenital) or develop later in life (acquired). Ptosis may be due to a myogenic, neurogenic, aponeurotic, mechanical or traumatic cause. Usually, ptosis occurs isolated, but may be associated with various other conditions, like immunological, degenerative, or hereditary disorders, tumors, or infections. Besides drooping, patients with ptosis complain about tired appearance, blurred vision, and increased tearing. Patients with significant ptosis may need to tilt their head back into a chin-up position, lift their eyelid with a finger, or raise their eyebrows. Continuous activation of the forehead and scalp muscles may additionally cause tension headache and eyestrain. If congenital ptosis is not corrected, amblyopia, leading to permanently poor vision, may develop. Patients with ptosis should be investigated clinically by an ophthalmologist and neurologist, for blood tests, X-rays, and CT/MRI scans of the brain, orbita, and thorax. Treatment of ptosis depends on age, etiology, whether one or both eyelids are involved, the severity of ptosis, the levator function, and presence of additional ophthalmologic or neurologic abnormalities. Generally, treatment of ptosis comprises a watch-and-wait policy, prosthesis, medication, or surgery. For minimal ptosis, Müller's muscle conjunctival resection or the Fasanella Servat procedure are proposed. For moderate ptosis with a levator function of 5-10 mm, shortening of the levator palpebrae or levator muscle advancement are proposed. For severe ptosis with a levator function <5 mm, a brow/frontalis suspension is indicated. Risks of ptosis surgery infrequently include infection, bleeding, over- or undercorrection, and reduced vision. Immediately after surgery, there may be temporary difficulties in completely closing the eye. Although improvement of the lid height is usually achieved, the eyelids may not appear perfectly symmetrical. In rare cases, full eyelid movement does not return. In some cases, more than one operation is required.

Adenosine A2A receptor antagonists are potential antidepressants: evidence based on pharmacology and A2A receptor knockout mice.

1. Adenosine, an ubiquitous neuromodulator, and its analogues have been shown to produce 'depressant' effects in animal models believed to be relevant to depressive disorders, while adenosine receptor antagonists have been found to reverse adenosine-mediated 'depressant' effect. 2. We have designed studies to assess whether adenosine A2A receptor antagonists, or genetic inactivation of the receptor would be effective in established screening procedures, such as tail suspension and forced swim tests, which are predictive of clinical antidepressant activity. 3. Adenosine A2A receptor knockout mice were found to be less sensitive to 'depressant' challenges than their wildtype littermates. Consistently, the adenosine A2A receptor blockers SCH 58261 (1 - 10 mg kg(-1), i.p.) and KW 6002 (0.1 - 10 mg kg(-1), p.o.) reduced the total immobility time in the tail suspension test. 4. The efficacy of adenosine A2A receptor antagonists in reducing immobility time in the tail suspension test was confirmed and extended in two groups of mice. Specifically, SCH 58261 (1 - 10 mg kg(-1)) and ZM 241385 (15 - 60 mg kg(-1)) were effective in mice previously screened for having high immobility time, while SCH 58261 at 10 mg kg(-1) reduced immobility of mice that were selectively bred for their spontaneous 'helplessness' in this assay. 5. Additional experiments were carried out using the forced swim test. SCH 58261 at 10 mg kg(-1) reduced the immobility time by 61%, while KW 6002 decreased the total immobility time at the doses of 1 and 10 mg kg(-1) by 75 and 79%, respectively. 6. Administration of the dopamine D2 receptor antagonist haloperidol (50 - 200 microg kg(-1) i.p.) prevented the antidepressant-like effects elicited by SCH 58261 (10 mg kg(-1) i.p.) in forced swim test whereas it left unaltered its stimulant motor effects. 7. In conclusion, these data support the hypothesis that A2A receptor antagonists prolong escape-directed behaviour in two screening tests for antidepressants. Altogether the results support the hypothesis that blockade of the adenosine A2A receptor might be an interesting target for the development of effective antidepressant agents.

Effects of amantadine on modification of dopamine dependent behaviours by molindone.

Amantadine, a dopamine agonist is reported to act by releasing dopamine from the dopaminergic nerve terminals as an anti-Parkinsonian drug. In the present behavioural study in the rat, molindone-induced catalepsy and ptosis, which are dopamine dependent-behaviors are reversed by amantadine. Amantadine has also revered molindone-induced inhibition of traction response in mice. Our study indicates that amantadine, like other DA agonists, e.g. amphetamine and apomorphine can antagonize or even reverse the neuroleptic induced dopaminergic behaviors.

Study of the antidepressant activity of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives.

A series of 23 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives were tested for acute toxicity and antidepressant activity in mice. Eight of the 23 compounds tested clearly antagonised the tetrabenazine effects and four of them (5, 7, 19, 23) showed activity values ranging from 40 to 75%, close to those shown by imipramine and viloxazine, the drugs chosen as reference standards. Compounds 7, 19 and 23 were also notably effective in the Porsolt test, shortening the immobility period of mice by more than 20%. The values obtained were very close to those elicited by imipramine and viloxazine. The most effective compounds in these tests were found among those bearing a primary amine or a benzoylamino group at the position 3 of the thieno[2,3-d]pyrimidine general structure (7, 19 and 23). The substitution of the thioxocarbonyl group at position 2 by a methylmercapto substituent maintained the activity (23). Compounds 7, 19 and 23 were chosen as prototypes for the design of new molecules with better antidepressant activity. These compounds did not present the adverse anticholinergic effects found in most tricyclic antidepressant drugs.

Preventing ptosis after botulinum treatment.

In a series of 33 blepharospasm patients who had the side effect of ptosis following therapeutic botulinum toxin type A (Botox: Allergan, Inc., Irvine, CA, U.S.A.) injection, we administered 41 injections of human botulinum immune globulin (IG) following injections of the toxin to test the dosage and timing of IG injection and its effectiveness in limiting or avoiding ptosis. An IG dose of 3.2 x 10(-3) international units (IU) per unit of Botox was effective in blocking toxin effect when injected into the same tissue site within 4 hours. An IG dose of 1.6 x 10(-2) to 3.2 x 10(-2) into the levator of the eye having more frequent ptosis in 19 patients reduced the incidence of ptosis to 11%. The fellow (control) eye had a ptosis incidence of 37%. No orbital hemorrhage or other adverse effect occurred from the IG or its injection.

[Efficacy of the lithium compound with prolonged action during "reserpine depression"]. / Effektivnost' soedinenii litiia s prolongirovannym deistviem pri "rezerpinovoi depressii".

A single administration of the new lithium compound with prolonged action formed on the basis of lithium oxyburate produces an antiblepharoptosis effect in rats with reserpine depression for 24 to 48 h. It optimally prevents the development of "reserpine-desynchronization" in rats when prescribed in the morning at intervals of 48 h.

[Amblyopia, refractive errors and strabismus in congenital ptosis]. / Amblyopie, Refraktionsfehler und Strabismus bei kongenitaler Ptosis.

The incidence of amblyopia in the normal population is 2-6%, whereas among patients with congenital ptosis it can be as high as 50%. We reviewed 146 cases of congenital ptosis in patients aged between 5 months and 15 years and compared them to a control group of 34 age- and sex-matched patients. In 78 children (156 eyes) reliable optotype visual acuity could be obtained. Fifty-three eyes (34%) were amblyopic. Ametropia was responsible for 34% and anisometropia for 28.3% of the amblyopia cases. In 25.4% of cases strabismus, and in 11.34% stimulus deprivation, was the reason for the development of amblyopia. Children with congenital ptosis should have retinoscopy done in cycloplegia, and refractive errors should be corrected early. Controlled patching therapy should also be started early. Since stimulus deprivation amblyopia is rare, congenital ptosis need not be corrected early in life.

Serotonergic activity of HP 184: does spontaneous release have a role?

Examination of HP 184, [N-n-propyl)-N-(3-fluoro-4-pyridinyl) -1H-3-methylindodel-1-amine hydrochloride], in a variety of tests for serotonergic activity revealed some unique properties of this compound. We report here that 100 microM HP 184 enhanced spontaneous release of [3H]serotonin (5-HT) from rat hippocampal slices. This release was independent of the uptake carrier. In vivo assays confirmed that HP 184 (20 mg/kg, i.p.) lacked significant interactions at the norepinephrine (NE) or 5-HT uptake carrier itself. Notably, HP 184 (15 mg/kg, i.p.) reduced drinking behavior in schedule-induced polydipsic (SIP) rats. We previously reported that some selective 5-HT reuptake inhibitors decrease SIP 30-40% after a 14-21 day treatment. In the current study, HP 184 decreased SIP beginning with the first treatment, and this reduction (30%) was maintained for 28 days. We further investigated HP 184 and serotonin metabolite levels. One hour after i.p. administration of 30 mg/kg HP 184, the ratio of whole brain 5-hydroxyindolacetic acid (5-HIAA) to 5-HT was increased, suggesting serotonergic activation. Under these conditions, the brain:plasma ratio of HP 184 was approximately 2:1, with brain concentrations of 1.6 micrograms/gram. We speculate that the spontaneous release effects of HP 184 may be responsible for the behavioral effects observed.