The Effect of Depressor Anguli Oris Muscle Block on Facial Symmetry in Synkinetic Facial Paralysis Patients and Its Role in Preoperative Assessment.

BACKGROUND: Depressor anguli oris muscle hypertonicity in synkinetic facial paralysis patients may have an overpowering antagonistic effect on facial symmetry. Depressor anguli oris muscle block is a crucial diagnostic test before any treatment planning. Presented is the largest patient cohort analysis to date on static and dynamic facial symmetry changes after depressor anguli oris muscle block. METHODS: Unilateral synkinetic patients with depressor anguli oris muscle hypertonicity were included. Resting symmetry and smile modiolus angle, excursion, and exposure of teeth were measured on both synkinetic and healthy hemifaces before and after depressor anguli oris muscle block using Emotrics and FaceGram photographic analyses. RESULTS: Thirty-six patients were included. Before depressor anguli oris block, resting modiolus height was elevated on the synkinetic side (p = 0.047). During open-mouth smile, reduced modiolus angle (p < 0.0001), modiolus excursion (p < 0.0001), and exposure of teeth (p < 0.0001) were observed on the synkinetic hemiface. After depressor anguli oris block, resting modiolus height became symmetric (p = 0.64). During open-mouth smile, modiolus angle and exposure of teeth significantly increased (both p < 0.0001); excursion did not improve on the synkinetic side (p = 0.13) but unexpectedly improved in open-mouth smile on the healthy side (p = 0.0068). CONCLUSIONS: Depressor anguli oris muscle block improved resting symmetry and modiolus angle and exposure of teeth during smile, demonstrating the inhibitory mimetic role of a hypertonic depressor anguli oris muscle in synkinesis. It is a critical diagnostic and communication tool in the assessment and treatment planning of depressor anguli oris muscle hypertonicity, suggesting the potential effects of future depressor anguli oris myectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Botulinum toxin type A (Botox) for the neuromuscular correction of excessive gingival display on smiling (gummy smile).

INTRODUCTION: Previously, botulinum toxin type A (BTX-A) (Botox; Allergan, Irvine, Calif) was shown to be effective in reducing excessive gingival display in 5 patients with gummy smiles. This study was conducted to determine whether the doses and the primary injection sites used in the pilot study for the correction of gummy smiles provide consistent, statistically significant, and esthetically pleasing results. METHODS: Thirty patients received BTX-A injections to reduce excessive gingival display. Gingival display was defined as the difference between the lower margin of the upper lip and the superior margin of the right incisor. Patients were followed at 2, 4, 8, 12, 16, 20, and 24 weeks postinjection, with changes documented by photographs and videos. At week 2, the patients rated the effects of BTX-A. A group of specialty clinicians also evaluated the effects of BTX-A. RESULTS: Preinjection gingival display averaged 5.2 +/- 1.4 mm in the 30 patients. At 2 weeks postinjection, mean gingival display had declined to 0.09 mm (+/- 1.06 mm) in 30 patients (t = 26.01, P <.00001). The average lip-drop at 2 weeks was 5.1 mm for 30 patients. Gingival display gradually increased from 2 weeks postinjection through 24 weeks, but, at 24 weeks, average gingival display had not returned to baseline values. Based on predictions from a third-order polynomial equation, the baseline average of 5.2 mm would not be reached until 30 to 32 weeks postinjection. Patients and specialty evaluators rated the effects of BTX-A as highly favorable. CONCLUSIONS: BTX-A injections for the neuromuscular correction of gummy smiles caused by hyperfunctional upper lip elevator muscles was effective and statistically superior to baseline smiles, although the effect is transitory.

Trospium chloride in patients with neurogenic detrusor overactivity: is dose titration of benefit to the patients?

OBJECTIVE: To determine whether dose titration based on therapeutic response is superior to standard dosing of oral trospium chloride in patients with neurogenic detrusor overactivity and, moreover, to investigate the possible underlying causes of differences in efficacy at equal doses in some patients. PATIENTS AND METHODS: Using a double-blind approach, two groups (standard dose and adjustable dose) with a total of 80 patients were treated with trospium chloride coated tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied depending on change ofurodynamic parameters defined as therapeutic response. In Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose group, it was permissible to increase the daily dose to 90 or 135 mg/day depending on the urodynamic treatment response. In contrast, doses remained unchanged in the standard dose group although a need for dose adjustment had been recognized under the double-blind conditions. Therapeutic response was defined as improvement of at least two of the following three urodynamic parameters: bladder compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were defined as secondary efficacy variables. Primary and secondary parameters were assessed by comparing baseline values with those at the end of treatment. Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann-Whitney U-test was used for secondary parameters. Trospium plasma concentration was measured to assess patient's compliance and as a tool to elucidate possible factors influencing treatment efficacy. Safety and tolerability were evaluated based on withdrawal rates and adverse events. RESULTS: Both dose groups had comparable baseline characteristics. Therapeutic response was achieved in 58% of patients in the adjustable dose group (ADG) and in 72% of those in the standard dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric capacity and bladder compliance were observed, and there was a clear decrease in detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all patients in the adjustable dose group and (seemingly) in 32.5% of those of the standard dose group. Further dose escalation after Day 14 was assessed as necessary in 15% of the standard dose group and 22% of the adjustable dose group. The main changes in urodynamic parameters occurred during the first 7 days of treatment, but in some patients it takes a longer time. No statistically significant differences between plasma trospium chloride levels in the two dose groups were observed at any time, but increase of plasma concentration with higher doses became obvious when patients were differentiated to individual dose stages. In both groups, the most common treatment-related adverse event was dry mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates of other adverse events such as dry skin, dysopia, increased heart rate and gastrointestinal disorders were much lower. CONCLUSION: Generally, in patients with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can be considered as being the standard dose, and dose adjustment, e.g. due to increased body weight, might usually not be necessary. However, increased daily doses of up to 135 mg appear to be safe when prescribed in individual patients less responsive to the drug.

Botulinum toxins in dentistry--the new paradigm for masticatory muscle hypertonicity.

A variety of factors, such as stress, hormones, diet, drugs, trauma, and certain neuromuscular diseases, can lead to an increase in sympathetic muscle tone, which results in masticatory muscle hypertonicity and parafunction. Dentists have traditionally attempted to treat and prevent this transient disease with methods that are expensive, risky, irreversible, and not evidence-based. There is a need for a conservative reversible noninvasive treatment that is quick, easy, relatively inexpensive, long acting, and effective. Botulinum toxin, a natural protein, is one of the most potent biological substances known. Masticatory muscle relaxation can be reliably achieved by injecting measured doses of botulinum toxin into specific sites in the major muscles of mastication. A reduction in dystonia and pain with optimization of function is easily achievable with a site- and dose-specific injection protocol. The use of botulinum toxin offers the dentist an extremely effective tool to add to the armamentarium for treating conditions that derive from masticatory and other pericranial muscular conditions, and offers the general dentist who is not an expert in gnathology and occlusion a safe, effective treatment for controlling the symptoms of masticatory muscle hypertonicity.

[Therapy for overactive detrusor using propiverine]. / Therapie der Detrusorhyperaktivität mit Propiverin.

BACKGROUND: Our aim was to evaluate the efficacy and tolerability of propiverine hydrochloride (propiverine) in daily practice and to check the risk-benefit relation using previously collected data on 4,390 patients. PATIENTS AND METHODS: A total of 2,932 patients with symptoms of overactive bladder were treated with propiverine over a period of 12 weeks using a multicentre post marketing surveillance. At three visits (inclusion, after 4 weeks, after 12 weeks), parameters from the micturition diary (incontinence episodes, frequency of micturition, micturition volume) were recorded. RESULTS: The number of incontinence episodes during daytime decreased during therapy from 3.6+/-3.8 to 1.2+/-2.3. The number of episodes at night decreased from 1.5+/-2.1 to 0.4+/-0.8 (both P<0.001). The mean volume per micturition improved during therapy (from 142.7 ml to 213.3 ml; +49.5%; P<0.0001). Some 85% of the investigators judged the efficacy of propiverine to be good or very good, 2.1% as not sufficient. The most frequent adverse event was dry mouth (17.3% of the patients after 12 weeks) mostly with low severity. More than 70% of the patients reported good or very good tolerability. Only 0.6% of the patients reported insufficient tolerability.

New indications for botulinum toxin type a in cosmetics: mouth and neck.

Botulinum toxin type A is frequently used to smooth hyperkinetic lines in the periocular and forehead areas of the upper face, but it has been used less frequently for indications in the lower face and neck. This study was designed to determine whether botulinum toxin treatment of the mouth and neck areas is as clinically successful as the treatment of the upper face. This was a retrospective study of patients who were treated with botulinum toxin type A (Botox) to soften hyperkinetic facial wrinkles. Of 100 patients randomly selected from a single clinical practice, 91 met the inclusion criteria and were divided into two groups for analysis. The 56 patients in group 1 did not receive treatment in the mouth and neck areas, whereas the 35 patients in group 2 were treated at least once in the mouth and neck areas. Patients were surveyed for periods ranging from 7 to 49 months. Most patients in each group had a single botulinum procedure during this period. Both groups of patients had comparable improvement of wrinkles both at the evaluation immediately after the neuromuscular blockade and during follow-up. In comparison with patients whose treatment was confined to the upper face, patients who received global treatment with botulinum toxin type A, including injections in the mouth and neck areas, were injected in more sites per procedure and had more procedures in combination with other therapies. Patient satisfaction with botulinum toxin treatment and outcomes was high in both groups. Botulinum toxin type A is an important tool within the therapeutic spectrum for the treatment of hyperkinetic facial wrinkles, including those in the areas of the mouth and neck.

[New pharmacological treatment concepts for overactive bladder]. / Neue pharmakologische Therapiekonzepte bei instabiler Blase.

Muscarinic receptor antagonists such as oxybutynin, propiverine, tolterodine, or trospium are the basis of medical treatment for overactive bladder. While they are moderately efficacious, their use can be limited by adverse effects such as dry mouth. This has sparked the search for new treatment options. Vanilloid receptor agonists, tachykinin receptor antagonists, potassium channel openers, and beta(3)-adrenoceptor agonists are currently under investigation, but are unlikely to become clinically available in the next few years. Therefore, current attempts to optimize treatment focus on improvement of existing drugs by new pharmaceutical formulations. Indeed, extended release formulations of oxybutynin (not available in Germany) or tolterodine have demonstrated an improved tolerability in clinical studies which was accompanied by an efficacy at least equal to that of their standard formulations.

Effect of spinal cord injury and of intrathecal baclofen on brainstem reflexes.

Reorganization of neural circuits within the central nervous system following injury appears to be a means of compensatory mechanism for loss of function. Reorganization following spinal cord injury is known to evoke changes at the cortical and spinal cord levels. Recent studies, however, provide evidence of enhanced brainstem reflexes and alterations in excitatory and inhibitory interneuronal brainstem circuits, suggesting that reorganization following spinal cord injury occurs also at the brainstem level. Reversal of these changes by continuous intrathecal baclofen infusion to normal levels or beyond indicates strong GABAergic involvement. Rapid changes in the blink reflex and its prepulse inhibition following intrathecal baclofen bolus application that parallel clinical changes in muscle hypertonia suggest a muscle tone regulating effect of baclofen at the brainstem level. Enhanced brainstem reflexes in spinal cord injury patients may be the consequence of decreased GABA-mediated inhibition and/or strengthening of facilitatory connections due to either direct or indirect plastic changes occurring at the brainstem level. Modulation of brainstem reflexes by baclofen may foster the understanding of pathophysiological mechanisms underlying diseases with increased brainstem activity. Rehabilitation after central nervous system injury will always be a challenge, but understanding the mechanisms of reorganization of undamaged neural pathways may help to develop better strategies for enhancing neuronal plasticity and for implementing neuronal reorganization into carefully planned therapy.

Effect of transdermal clonidine on spinal spasticity. A case series.

Clonidine, a centrally acting alpha 2 receptor adrenergic agonist, has been successfully used as adjunctive therapy in patients with spinal cord injury with problematic spasticity not adequately controlled by recognized spasmolytic agents. A transdermal system providing approximately constant and continuous systemic delivery of clonidine has been recently introduced to enhance patient compliance. However, experience with transdermal clonidine in the management of spasticity is limited. Three cases are presented of patients with spasticity as the result of cervical spinal cord injury, inadequately managed by oral baclofen, in whom transdermal clonidine was administered. Significant improvement in spastic hypertonia was observed in all three cases. Transdermally delivered clonidine was well tolerated, with reported side effects limited to dryness of the mouth.

Aesthetic botulinum A toxin in the mid and lower face and neck.

BACKGROUND: Botulinum toxin type A (BOTOX formulation) is used extensively for smoothing hyperkinetic lines in the upper face. The use of botulinum toxin for aesthetic indications in the mid and lower face and neck is now becoming increasingly popular. OBJECTIVE: To review our current approaches to botulinum toxin treatment for cosmetic indications in the mid and lower face and neck. METHODS: Procedures and outcomes are described for the primary and adjunctive use of botulinum toxin. RESULTS: Cosmetic treatment with botulinum toxin successfully changes the contour of the palebral aperture; smoothes lines, including "bunny" lines, perioral rhytides, and horizontal neck lines; softens creases, including the mental crease and melomental folds; and alleviates facial asymmetry and nasal flare. The doses of botulinum toxin used in the mid and lower face are generally lower than those used in the upper face. Caution must be used in injecting botulinum toxin in the perioral area to avoid an incompetent mouth. CONCLUSION: Botulinum toxin treatment is valuable for aesthetic improvements in the mid and lower face and neck. In some areas, particularly the perioral region, the use of botulinum toxin in combination with other therapeutic modalities provides optimal results.

Efficacy and safety of transdermal oxybutynin in patients with urge and mixed urinary incontinence.

PURPOSE: We evaluated the efficacy and safety of an oxybutynin transdermal delivery system (TDS) in a general population of patients with overactive bladder and urge or mixed urinary incontinence. MATERIALS AND METHODS: Following symptom stabilization or treatment withdrawal 520 adult patients were randomized to 12 weeks of double-blind daily treatment with 1.3, 2.6 or 3.9 mg. oxybutynin TDS or placebo administered twice weekly, followed by a 12-week open-label, dose titration period to assess efficacy and safety further. Evaluations included patient urinary diaries, incontinence specific quality of life and safety. RESULTS: A dose of 3.9 mg. daily oxybutynin TDS significantly reduced the number of weekly incontinence episodes (median change -19.0 versus -14.5, p = 0.0165), reduced average daily urinary frequency (mean change -2.3 versus -1.7, p = 0.0457), increased average voided volume (median change 24 versus 6 ml., p = 0.0063) and significantly improved quality of life (Incontinence Impact Questionnaire total score, p = 0.0327) compared with placebo. Average voided volume increased in the daily 2.6 mg. group (19 ml., p = 0.0157) but there were no other significant differences between 1.3 and 2.6 mg. oxybutynin TDS and placebo. The most common adverse event was application site pruritus (oxybutynin TDS 10.8% to 16.8%, placebo 6.1%). Dry mouth incidence was similar in both groups (7.0% versus 8.3%, p not significant). In the open-label period a sustained reduction of nearly 3 incontinence episodes per day was reported for all groups. CONCLUSIONS: Doses of 2.6 and 3.9 mg. oxybutynin TDS daily improve overactive bladder symptoms and quality of life, and are well tolerated. Transdermal oxybutynin is an innovative new treatment for overactive bladder.

Polyethylene glycol 3350 for constipation in children with dysfunctional elimination.

PURPOSE: Children with daytime wetting often have constipation, and treatment of constipation helps children become dry. Polyethylene glycol 3350 (Miralax, Braintree Laboratories, Braintree, Massachusetts) is a nonaddictive, tasteless powder that can be mixed with any liquid for treatment of constipation. MATERIALS AND METHODS: We review our use of polyethylene glycol 3350 in 35 girls and 11 boys with dysfunctional elimination. Noninvasive urodynamic studies and post-void residual measurement were performed before and during treatment. RESULTS: A significant increase in frequency of bowel movements occurred while taking polyethylene glycol 3350 (p = 0.0001). Average final dose was 0.63 gm/kg. The only reported adverse effect was diarrhea (9 patients). Of the children 18 became dry, 26 had decreased wetting and 2 had no improvement. Voided volume increased (146 vs 210 ml, p <0.0001) and post-void residual decreased significantly (92 vs 48 ml, p <0.0001) while on polyethylene glycol 3350. Ten children were still considered constipated including both patients who experienced no change in wetting. Average final dose in this group (0.69 gm/kg) did not differ significantly from those in whom constipation resolved (0.61 gm/kg). Patients in whom constipation resolved had a significantly lower post-void residual than those who remained constipated (11.8% vs 30.6%, p <0.01) and were significantly more likely to become dry or improved (p = 0.045). CONCLUSIONS: The efficacy, compliance and lack of significant side effects make polyethylene glycol 3350 an ideal substance for treatment of constipation in children with dysfunctional elimination. Persistent constipation was associated with decreased resolution of voiding symptoms and significantly increased post-void residuals.

Cyproheptadine for intrathecal baclofen withdrawal.

OBJECTIVE: To evaluate the efficacy of cyproheptadine in the management of acute intrathecal baclofen (ITB) withdrawal. DESIGN: Descriptive case series. SETTING: University hospital with a comprehensive in- and outpatient rehabilitation center. PARTICIPANTS: Four patients (3 with spinal cord injury, 1 with cerebral palsy) with implanted ITB infusion pumps for treatment of severe spasticity, who had ITB withdrawal syndrome because of interruption of ITB infusion. INTERVENTIONS: Patients were treated with 4 to 8mg of cyproheptadine by mouth every 6 to 8 hours, 5 to 10mg of diazepam by mouth every 6 to 12 hours, 10 to 20mg of baclofen by mouth every 6 hours, and ITB boluses in some cases. MAIN OUTCOME MEASURES: Clinical signs and symptoms of ITB withdrawal of varying severity were assessed by vital signs (temperature, heart rate), physical examination (reflexes, tone, clonus), and patient report of symptoms (itching, nausea, headache, malaise). RESULTS: The patients in our series improved significantly when the serotonin antagonist cyproheptadine was added to their regimens. Fever dropped at least 1.5 degrees C, and heart rate dropped from rates of 120 to 140 to less than 100bpm. Reflexes, tone, and myoclonus also decreased. Patients reported dramatic reduction in itching after cyproheptadine. These changes were associated temporally with cyproheptadine dosing. DISCUSSION: Acute ITB withdrawal syndrome occurs frequently in cases of malfunctioning intrathecal infusion pumps or catheters. The syndrome commonly presents with pruritus and increased muscle tone. It can progress rapidly to high fever, altered mental status, seizures, profound muscle rigidity, rhabdomyolysis, brain injury, and death. Current therapy with oral baclofen and benzodiazepines is useful but has variable success, particularly in severe cases. We note that ITB withdrawal is similar to serotonergic syndromes, such as in overdoses of selective serotonin reuptake inhibitors or the popular drug of abuse 3,4-methylenedioxymethamphetamine (Ecstasy). We postulate that ITB withdrawal may be a form of serotonergic syndrome that occurs from loss of gamma-aminobutyric acid B receptor-mediated presynaptic inhibition of serotonin. CONCLUSION: Cyproheptadine may be a useful adjunct to baclofen and benzodiazepines in the management of acute ITB withdrawal syndrome.