[How to treat spasticity after stroke ?] / Comment je traite la spasticité après un accident vasculaire cérébral.

Spasticity is a form of hypertonia frequently encountered in patients who suffered from stroke and is a cause of functional limitation, contractures, osteoarticular deformations, pain and wounds. The first-line treatment of focal or multifocal spasticity consists in intramuscular injections of botulinum toxin type A in the muscles concerned, in association with positioning measures and physical therapy. Despite the fact this pathology is common, there is often a delay in the diagnosis, and consequently the treatment, leading to harmful consequences for the patient. In some specific indications, surgery can also be a therapeutic option. Finally, spasticity should be distinguished from other types of hypertonia, e.g. dystonia.

: La spasticité est une forme d'hypertonie, fréquemment rencontrée dans les suites d'un accident vasculaire cérébral. Elle peut être à l'origine de limitations fonctionnelles, de rétractions tendineuses, de déformations ostéoarticulaires, de douleurs et de plaies. Le traitement de première ligne de la spasticité focale ou multifocale repose sur l'injection intramusculaire de toxine botulique de type A dans les muscles entrepris, en association à des mesures de positionnement et à une prise en charge kinésithérapeutique. Malgré la fréquence de cette affection, elle est encore trop souvent reconnue, et donc traitée, tardivement, ce qui aboutit à des conséquences délétères pour le patient. Dans certaines indications précises, la chirurgie a également une place dans l'arsenal thérapeutique de la spasticité. Enfin, la spasticité ne doit pas être confondue avec les autres formes d'hypertonie, comme la dystonie.

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.

Fisurectomy and anoplasty with botulinum toxin injection in patients with chronic anal posterior fissure with hypertonia: a long-term evaluation.

Chronic anal fissure's (CAF) etiopathogenesis remain unclear. CAF of the posterior commissure (CAPF) are often characterized by internal anal sphincter (IAS) hypertonia. The treatment of this disease aimed to reduce IAS hypertonia. Due to the high rate of anal incontinence after LIS, the employment of sphincter preserving surgical techniques associated to pharmacological sphincterotomy appears more sensible. The aim of our study is to evaluate the long-term results of fissurectomy and anoplasty with V-Y cutaneous flap advancement associated to 30 UI of botulinum toxin injection for CAPF with IAS hypertonia. We enrolled 45 patients undergone to fissurectomy and anoplasty with V-Y cutaneous flap advancement and 30 UI botulinum toxin injection. All patients were followed up for at least 5 years after the surgical procedure, with evaluation of anal continence, recurrence rate and MRP (Maximum resting pressure), MSP (Maximum restricting pressure), USWA (Ultrasound wave activity). All patients healed within 40 days after surgery. We observed 3 "de novo" post-operative anal incontinence cases, temporary and minor; the pre-operative ones have only temporary worsened after surgery. We reported 3 cases of recurrences, within 2 years from surgery, all healed after conservative medical therapy. At 5 year follow-up post-operative manometric findings were similar to those of healthy subjects. At 5 years after the surgical procedure, we achieved good results, and these evidences show that surgical section of the IAS is not at all necessary for the healing process of the CAPF.

The 1316T>C missenses mutation in MTHFR contributes to MTHFR deficiency by targeting MTHFR to proteasome degradation.

5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare hereditary disease characterized by defects in folate and homocysteine metabolism. Individuals with inherited MTHFR gene mutations have a higher tendency to develop neurodegeneration disease as Alzheimer' disease and atherosclerosis. MTHFR is a rate-limiting enzyme catalyzing folate production, various SNPs/mutations in the MTHFR gene have been correlated to MTHFR deficiency. However, the molecular mechanisms underpinning the pathogenic effects of these SNPs/mutations have not been clearly understood. In the present study, we reported a severe MTHFR deficiency patient with late-onset motor dysfunction and sequenced MTHFR gene exons of the family. The patient carries an MD-associating SNP (rs748289202) in one MTHFR allele and the rs545086633 SNP with unknown disease relevance in the other. The rs545086633 SNP (p.Leu439Pro) results in an L439P substitution in MTHFR protein, and drastically decreases mutant protein expression by promoting proteasomal degradation. L439 in MTHFR is highly conserved in vertebrates. Our study demonstrated that p.Leu439Pro in MTHFR is the first mutation causing significant intracellular defects of MTHFR, and rs545086633 should be examined for the in-depth diagnosis and treatment of MD.

Surgical Sphincter Saving Approach and Topical Nifedipine for Chronic Anal Fissure with Hypertonic Internal Anal Sphincter.

PURPOSE: The role of augmented internal anal sphincter (IAS) tone in the genesis of posterior chronic anal fissure (CAPF) is still unknown. Lateral internal sphincterotomy is the most employed surgical procedure, nevertheless it is burdened by high risk post-operative anal incontinence. The aim of our study is to evaluate results of sphincter saving procedure with post-operative pharmacological sphincterotomy for patients affected by CAPF with IAS hypertonia. Methods: We enrolled 30 patients, undergone fissurectomy and anoplasty with V-Y cutaneous flap advancement; all patients received topical administration of nifedipine 0.3% and lidocaine 1.5% ointment-based therapy before and for 15 days after surgery. The primary goal was patient's complete healing and the evaluation of incontinence and recurrence rate; the secondary goal included the evaluation of manometry parameters, symptom relief and complications related to nifedipine and lidocaine administration. Results: All wounds healed within 40 days after surgery. We didn't observe any de novo postoperative anal incontinence case. We reported 2 cases of recurrences, healed after conservative therapy. We didn't report any local complications related to the administration of the ointment therapy; with whom all patients reported a good compliance. Conclusions: Fissurectomy and anoplasty with V-Y cutaneous advancement flap and topical administration of nifedipine and lidocaine, is an effective treatment for CAPF with IAS hypertonia.

Analgesic injection of botulinum toxin in anal fissures is efficient and can be performed safely in patients actively receiving chemotherapy.

PURPOSE: Injection of botulinum toxin into the internal anal sphincter is a well-documented intervention to reduce anal hypertonia in the treatment of anal fissures. In patients receiving chemotherapy, painful anal conditions are frequent, secondary to change in bowel habits and reduced immunity. However, injection of botulinum toxin is often not offered due to fear of complications. METHODS: In this retrospective longitudinal observational study, performed in a tertiary hospital setting, we analysed patient characteristics, outcome and complication rates of botulinum toxin injection in patients actively receiving chemotherapy. RESULTS: Twenty-six patients were treated with 20-50 IU botulinum toxin while actively receiving chemotherapy because of intractable pain and hypertonia. The fissure was located dorsally in 69% (n = 18) and ventrally in 19% (n = 5), while in 3 patients (12%), no fissure was documented. The majority of the patients (88%, n = 23) had complete (54%, n = 14) or partial (35%, n = 9) relief of pain. In three patients, additional anal pathology developed in the weeks following botulinum toxin injection: thrombosis of grade IV haemorrhoids, perianal haematoma and an intersphincteric abscess. CONCLUSIONS: Injection of botulinum toxin in the anal sphincters is a safe and effective analgesic option in patients with anal fissure while actively receiving chemotherapy.

Transvaginal Trigger Point Injections Improve Pain Scores in Women with Pelvic Floor Hypertonicity and Pelvic Pain Conditions.

OBJECTIVES: Chronic pelvic pain in women often requires multimodal treatment regimens. We describe our method of transvaginal trigger point injections (TPIs) and report outcomes using change in pain scores. METHODS: This was a retrospective review of women treated with in-office pelvic floor muscle injections from January 2012 to August 2015. Lidocaine 1% and 2%, bupivacaine 0.5%, or ropivacaine 0.5% with or without the addition of triamcinolone 40 mg was used for the injections. Pain was reported on a 0- to 10-point numerical rating scale before and after injection. Differences in pretreatment and posttreatment pain scores were analyzed after the first injection and after subsequent injections. Repeated-measures analysis was used to determine if any variable affected treatment response. RESULTS: One hundred one women with a mean age of 44 years had a total of 257 separate visits for pelvic floor muscle injections. Triamcinolone was used at 90.2% (230/255) of the TPI visits. After the initial TPI visit, there was significant decrease in total levator numerical rating scale score (maximum score, 20; mean, -6.21 ± 4.7; P < 0.0001), and 77% (70/91) of patients had improved. These significant improvements were noted at all visits 1 through 4 and whether bilateral or unilateral injections were done. Only the total amount of local anesthestic used had a significant effect on the change in total levator pain scores (P = 0.002). Minor adverse effects including leg numbness, dizziness, nausea, bleeding, and headache occurred at 10% of visits. CONCLUSIONS: Pelvic floor muscle injections decrease pain levels in women with pelvic floor dysfunction.

Factors that influence the urodynamic results of botulinum toxin in the treatment of neurogenic hyperactivity.

OBJECTIVES: To determine the urodynamic efficacy and factors that influence the urodynamic results of treatment of neurogenic detrusor hyperactivity with intradetrusor injection of botulinum toxin type A (BTX-A) in patients with spinal cord injury (SCI). MATERIAL AND METHODS: A retrospective study was conducted with a cohort of 70 patients composed of 40 men and 30 women with stable SCI (mean age, 39 ± 13.3 years) who underwent an intradetrusor injection of 300 IUs of BTX-A. A urodynamic study was conducted prior to the injection and 6 ± 4.3 months after the treatment. New urodynamic studies were subsequently performed up to an interval of 16 ± 12.2 months. RESULTS: The BTX-A significantly increased (p < .05) the cystomanometric bladder capacity, the bladder volume of the first involuntary contraction of the detrusor and the postvoid residue. We observed a decrease that tended towards statistical significance (p < .1) of the maximum detrusor pressure and the maximum urine flow. Neither the bladder accommodation nor the urethral resistance index (bladder outlet obstruction index) varied significantly. The increase in vesical capacity was maintained in 50% of the sample for more than 32 months. Age, sex, anticholinergic treatment and lesion age showed no influence in terms of the increase in bladder capacity. The indwelling urinary catheter (IUC) was the only statistically significant negative factor. CONCLUSIONS: The urodynamic effect of BTX-A is maintained for a considerable time interval. The IUC negatively influences the result of the treatment.

Pediatric tone management.

Tone management is one of the primary roles of a pediatric physiatrist. Hypertonicity frequently inhibits normal movement patterns in children with central nervous system lesions but at times can reinforce muscle group firing and be useful for a child's function. Treatment approaches should be individualized based on functional goals, degree of impairment, interference with care, and type and location of hypertonicity. Treatment plans should be created in collaboration with all individuals caring for the child. There are many causes of hypertonicity as well as many nonsurgical and surgical treatments. Historical and current evidence-based treatments are reviewed.

Rapamycin attenuates bladder hypertrophy during long-term outlet obstruction in vivo: tissue, matrix and mechanistic insights.

PURPOSE: Previous molecular studies showed that the mTOR inhibitor rapamycin prevents bladder smooth muscle hypertrophy in vitro. We investigated the effect of rapamycin treatment in vivo on bladder smooth muscle hypertrophy in a rat model of partial bladder outlet obstruction. MATERIALS AND METHODS: A total of 48 female Sprague-Dawley® rats underwent partial bladder outlet obstruction and received daily subcutaneous injections of rapamycin (1 mg/kg) or vehicle commencing 2 weeks postoperatively. A total of 36 rats underwent sham surgery and received rapamycin or vehicle. Rats were sacrificed 3, 6 and 12 weeks after surgery. Before sacrifice, voiding was observed in a metabolic cage for 24 hours. Bladder-to-body weight in gm bladder weight per kg body weight and post-void residual urine were assessed. We evaluated Col1a1, Col3a1, Eln and Mmp7 mRNA expression and histology. Two-factor ANOVA and the post hoc t test were applied. RESULTS: Bladder outlet obstruction caused a significant increase in bladder weight in all obstructed groups. Three weeks postoperatively (1 week of treatment) there was no difference in the bladder-to-body weight ratio in the obstructed group. However, at 6 and 12 weeks (4 and 10 weeks of treatment, respectively) the bladder-to-body weight ratio of rats with obstruction plus rapamycin was significantly lower than that of rats with obstruction plus vehicle. Post-void residual urine volume after 6 and 12 weeks of obstruction was lower in obstructed rats with rapamycin compared to that in obstructed rats with vehicle. Rapamycin decreased the obstruction induced expression of Col1a1, Col3a1, Eln and Mmp7. CONCLUSIONS: Rapamycin prevents mechanically induced hypertrophy in cardiovascular smooth muscle. In vivo mTOR inhibition may attenuate obstruction induced detrusor hypertrophy and help preserve bladder function.

Detrusorectomy reduces the need for augmentation and use of antimuscarinics in children with neuropathic bladders.

OBJECTIVE: To assess bladder behaviour and long-term outcome after detrusorectomy in children. MATERIAL AND METHODS: Between 1990 and 2001, 49 detrusorectomies were performed (mean follow-up: 9.6 years) in children with neuropathic bladders (mean age at surgery: 9.8 years). Urodynamic study (UDS) was done before surgery (pre-UDS) and after surgery (UDS-1 and UDS-2). Bladder behaviour was assessed as good, fair or poor depending on the volume and intravesical pressure. In all patients, oxybutynin and clean intermittent catheterization were used preoperatively. In 24 patients, good bladder compliance and capacity were seen before detrusorectomy. RESULTS: Good and fair outcomes were observed in 35 (71%) patients at 1 year and in 39 (79%) patients 6 years after detrusorectomy. In 30 (60%) patients, there was hardly any difference between the first and second follow-up. In 9 (18%) patients, formal bowel bladder augmentation was necessary: in 6 (12%) because of poor compliance and in 3 because of small bladder volume and incontinence. Seven patients improved during follow-up, 5 of them after resuming oxybutynin. In 11 patients, oxybutynin could be stopped, and in 2 the dosage could be reduced to once daily. CONCLUSIONS: The good short-term results of detrusorectomy generally remain unchanged at long-term follow-up. Detrusorectomy can reduce the need for antimuscarinics, and the need for formal bladder augmentation in selected cases.

Comparison of long-term outcomes of patients with severe traumatic or hypoxic brain injuries treated with intrathecal baclofen therapy for dysautonomia.

PRIMARY OBJECTIVE: To compare the long-term outcome of patients with severe traumatic brain injury and patients with hypoxic brain injury with dysautonomia and hypertonia treated with intrathecal baclofen therapy. METHODS AND PROCEDURES: Fifty-three patients with severe traumatic (n = 43/53) or hypoxic (n = 10/53) brain injuries treated by intrathecal baclofen therapy were included to be evaluated with the Coma Recovery Scale-Revised, the Barthel Index, the Glasgow Outcome Scale, the Ashworth scale, the scores of hypertonic attacks, of sweating episode and of voluntary motor responses. A retrospective analysis highlighted patients' characteristics at admission and before surgery and their complications. MAIN OUTCOMES AND RESULTS: After a mean follow-up time of 9.6 years, 13/53 (24.5%) patients had died. Alive patients with traumatic brain injury had a higher level of consciousness recovery (p < 0.02) and more abilities in activities of daily living (p < 0.008) in the long-term. Their dysautonomia and limb hypertonia also significantly improved, contrary to patients with hypoxic brain injury who needed higher doses of baclofen (p < 0.03). CONCLUSIONS: At long-term follow-up, patients with hypoxic brain injury had a poorer functional outcome than patients with traumatic brain injury with persistent symptoms of dysautonomia associated with uncontrolled hypertonia, despite the use of intrathecal baclofen.

Respiratory retraining therapy in long-term treatment of paradoxical vocal fold dysfunction.

OBJECTIVES: Paradoxical vocal fold dysfunction (PVFD) is a disorder in the larynx featuring involuntary adduction of the vocal folds during the inspiratory phase of breathing. The symptoms include acute episodes of dyspnea and bouts of coughing. To date, there is no universally acknowledged treatment for PVFD, though respiratory retraining therapy is the treatment of choice. AIMS: The purpose of this work was to evaluate the results of long-term respiratory retraining therapy in cases of PVFD. PATIENTS AND METHODS: We treated 20 patients with PVFD for 2 years: 10 subjects were submitted to a cycle of respiratory retraining therapy every 12 months (receiving a total of 3 cycles) while 10 were given a cycle every 3 months (for a total of 9 cycles) no matter what their clinical conditions were. RESULTS: The results show that long-term respiratory retraining is particularly efficacious if the cycles of treatment are repeated, no matter what clinical conditions are present. In fact, when only one cycle of retraining treatment is given a year, there is initial improvement followed by progressive worsening. CONCLUSIONS: Long-term respiratory rehabilitation is effective, especially if the treatment is given at least once every 3 months.

Fissurectomy combined with anoplasty and injection of botulinum toxin in treatment of anterior chronic anal fissure with hypertonia of internal anal sphincter: a pilot study.

BACKGROUND: In patients affected by anterior chronic anal fissure (CAAF) with hypertonia of the internal anal sphincter (IAS), the role of IAS hypertonia remains unclear. The aim of this study was to evaluate the efficacy of fissurectomy combined with advancement flap and IAS injection of botulinum toxin in healing the CAAF with hypertonia of IAS resistant to medical therapy. METHODS: Ten consecutive patients were enrolled. Anorectal manometry was performed preoperatively and at 6 months. CAAF with hypertonia was defined as those associated with maximum resting pressure (MRP) values higher than 85 mmHg. All patients underwent fissurectomy and anoplasty with advancement skin flap combined with the intrasphincter injection of 30 UI of botulinum toxin. Complete healing, MRP changes, relief of symptoms and immediate and long-term complications were recorded. RESULTS: Complete healing was observed in all patients within 30 days of the operation. The intensity and duration of pain post-defecation was reduced significantly starting from the first defecation. In all subjects, the preoperative MRP values were significantly reduced at 6 months. One month after surgery, three patients reported anal incontinence, two of them had complained preoperatively. The only postoperative complications were minor. CONCLUSIONS: Fissurectomy combined with advancement flap and intrasphincter injection of botulinum toxin results in complete healing, significant MRP reduction and full relief of symptom in all patients, thus it represents a valid procedure in preventing the occurrence of anal incontinence.

Botulinum toxin A prolongs functional durability of voice prostheses in laryngectomees with pharyngoesophageal spasm.

PURPOSE: Laryngectomized patients with pharyngoesophageal spasm frequently have poor voice quality and dysphagia. Local botulinum toxin A (BTA) injection can relieve muscular hypertonicity and improve symptoms. This procedure should also prolong the functional life span of the tracheoesophageal voice prosthesis. MATERIALS AND METHODS: This study evaluates 33 BTA treatments in 11 laryngectomees. All patients were having poor voice quality; 6 patients had additional dysphagia. In 10 patients, the BTA injection has been carried out during rigid pharyngoscopy under general anesthesia. One patient was treated in local anesthesia. RESULTS: A subjective improvement of voice quality was reported in 94%. This lasted on average for 20 weeks. The swallowing function improved moderately. For the first time, the functional life span of voice prostheses was examined. After treatment of pharyngoesophageal spasm, their durability was almost tripled. The BTA therapy has a significant effect. CONCLUSIONS: The BTA treatment improves voice quality and prolongs functional durability of voice prostheses in laryngectomees with pharyngoesophageal spasm. The success of treatment is of limited duration but can be repeated in the long-term.

Botulinum toxin in the treatment of OAB, BPH, and IC.

Botulinum neurotoxins (BoNTs) are well known for their ability to potently and selectively disrupt and modulate neurotransmission. BoNT is currently undergoing regulatory evaluation for urological disorders in the United States and the European Union and is not FDA approved for urologic use. Overactive bladder (OAB) and benign prostatic hyperplasia (BPH) are common urologic conditions characterized by urinary frequency, urgency, nocturia, urge incontinence and, in the case of BPH, decreased urine flow that are currently being evaluated in clinical trials with BoNT-A. Interstitial cystitis (IC) is a chronic condition in which patients describe urinary frequency, urgency and associated bladder/pelvic pain. In the two former conditions, BoNT-A is currently being evaluated in Phase II or Phase III clinical trials as a therapeutic agent. Evidence for BoNT in the treatment of IC is limited to small case series. The purpose of this article is to provide up to date clinical evidence regarding the use of BoNT to treat these three urologic problems. For the sake of clarity, BoNT-A describes the use of Botox unless otherwise specified. In addition, when describing OAB, two sub-populations exist: those with OAB of neurogenic origin (NDO) and those with OAB of unknown (idiopathic) origin (IDO).

Topical application of isosorbide dinitrate in patients with persistent constipation after pull-through surgery for Hirschsprung's disease.

AIMS: The aim of this study was to evaluate the anal manometric changes and the clinical effects after topical application of isosorbide dinitrate (ISDN) in patients with persistent constipation after pull-through surgery for Hirschsprung's disease (HD). METHODS: We studied 3 children (2 males and 1 female), aged 2, 3 and 5 years respectively, who had undergone the Soave-Boley surgical procedure for HD and who suffered from persistent constipation after operation. We performed a pre- and postoperative anorectal manometry study and we applied ISDN paste (1 mg/kg two times daily) in the anal region for three weeks. All patients were followed-up and re-evaluated at 1, 3, and 6 months. RESULTS: All patients showed an improvement of symptoms, with an average of 4 spontaneous evacuations per week. Prior to the topical treatment, the medium pressure was 115.6 mmHg (range 102 - 130 mmHg), the maximum pressure was 160 mmHg (range 145 - 175 mmHg), and the medium length of the high pressure zone was 1.8 cm (range 1.5 - 2.0 cm). At the 6 month follow-up, the medium pressure was 57.3 mmHg (range 52 - 61 mmHg, a decrease of 54.4 %), the maximum pressure was 98 mmHg (range 88 - 107 mmHg; a decrease of 38.7 %), and the medium length of the high pressure zone was 1.6 cm (range 1.4 - 1.8 cm; a decrease of 11.1 %). CONCLUSIONS: Topical treatment with ISDN is a valid therapeutic alternative to an anal myotomy in patients with persistent constipation after pull-through surgery for HD. However, a greater number of cases and a longer follow-up are necessary to confirm the validity of our experience.

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.

Weight gain in children with hypertonia of cerebral origin receiving intrathecal baclofen therapy.

OBJECTIVE: To identify the pattern of weight change in children receiving intrathecal baclofen (ITB) therapy. DESIGN: A retrospective medical chart review was conducted to identify weight status before and after ITB pump implantation. SETTING: Tertiary care children's hospital and academic medical center. PARTICIPANTS: All children and adolescents with hypertonia of cerebral origin who were younger than 19 years of age at the time of pump placement and followed in our pediatric baclofen pump program. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A linear mixed model was used to examine the rate of change in weight (weight-gain velocity) before and after surgery. Weight change was adjusted for age, sex, functional level determined by the Gross Motor Functional Classification System, tube feeding, dystonia, and other comorbidities. RESULTS: The average weight-gain velocity was 2.32 kg/y presurgery and 2.93 kg/y postsurgery, adjusted for potential confounders. The 0.61 kg/y increase in weight-gain velocity attained statistical significance (P = .028). CONCLUSIONS: Although excessive weight gain is not a common problem in children with cerebral origin spasticity, increased weight-gain velocity is prevalent in children receiving ITB therapy. Health care providers may anticipate a welcome weight gain in the underweight child. This consequence should be considered when managing children receiving ITB therapy, and health care providers must appropriately intervene to prevent excessive weight gain. Further studies exploring the reasons for the increased weight-gain velocity are warranted.