GABAergic drug use and global, cognitive, and motor functional outcomes after stroke.

BACKGROUND: In animal models and healthy volunteers, the use of GABA A receptor agonists (GABA-AGs) seem deleterious for functional recovery. The agents are widely used for subacute stroke, but their effect on functional recovery remains unclear. OBJECTIVES: We aimed to evaluate the association between GABA-AG use and functional recovery after stroke. METHODS: We retrospectively recruited 434 survivors of subacute stroke admitted for inpatient rehabilitation between 2000 and 2013 in our institution (107 with and 327 without GABA-AG use). We used multivariate regression to assess the association of GABA-AG use and successful functional recovery, defined as reaching, between admission and discharge, the minimal clinically important difference (MCID) of 22 points on the global Functional Independence Measure (FIM). Secondary analyses were the associations of GABA-AG with cognitive and motor FIM MCID and constant GABA-AG exposure (24h/24 GABA-AG) with global, cognitive and motor FIM MCID. A new estimation of the MCID was performed with the standard error of measurement. RESULTS: Reaching the global FIM MCID was associated with GABA-AG use (adjusted odds ratio [aOR] 0.54 [95% CI 0.31-0.91], P=0.02) as well as 24h/24 GABA-AG use (aOR 0.25 [0.08-0.83]; P=0.02). Furthermore, GABA-AG and 24h/24 GABA-AG use was inversely but not always significantly associated with reaching the cognitive FIM MCID (aOR 0.56, P=0.07; aOR 0.26, P=0.06, respectively) and motor FIM MCID (aOR 0.51, P=0.07; aOR 0.13, P=0.01, respectively). The estimated MCID was 19 for global FIM, 4 for cognitive FIM, and 16 for motor FIM. CONCLUSIONS: GABA-AG use is associated with not reaching successful functional recovery during stroke rehabilitation. Randomised trials are needed to formally establish the potential deleterious effect of GABA-AG use on functional recovery.

Mini invasive skeletal muscle biopsy technique with a tri-axial end cut needle.

OBJECTIVE: Skeletal Muscle Biopsy is a minor surgical procedure for the diagnosis of different neuromuscular pathological conditions and has recently gained popularity also in the research field of age-related muscular modifications and sarcopenia. Few studies focused on the application of mini-invasive muscular biopsy in both normal and pathological conditions. The aim of our study was to describe a mini invasive ultrasound-guided skeletal muscular biopsy technique in complete spinal cord injured (SCI) patients and healthy controls with a tri-axial end-cut needle. PATIENTS AND METHODS: Skeletal muscle biopsies were collected from 6 chronic SCI patients and 3 healthy controls vastus lateralis muscle with a tri-axial end cut needle (Biopince© - Angiotech). Muscle samples were stained for ATPase to determine fibers composition, moreover, gene expression of cyclooxygenase-1 (COX-1) and prostaglandin E2 receptor has been analyzed by Real Time RT-PCR. RESULTS: All the procedures were perfomed easily without failures and complications. Control tissue was macroscopically thicker than SCI one. Control specimen displayed an equal distribution of type I and type II fibers, while SCI sample displayed a prevalence of type II fibers SCI specimen displayed a significant reduction in COX-1 gene expression. This mini-invasive approach was easy, accurate and with low complication rate in performing skeletal muscle biopsy in both SCI patients and controls. CONCLUSIONS: This technique could be useful in conditions in which the overall quantity of specimen required is small like for molecular biology analysis. For histological diagnostic purposes and/or conditions in which the original tissue is already pathologically modified, this technique should be integrated with more invasive techniques.

Evaluation of serum myostatin and sclerostin levels in chronic spinal cord injured patients.

STUDY DESIGN: Case-control study. OBJECTIVES: To assess serum myostatin levels, bone mineral density (BMD), appendicular skeletal muscle mass (ASMM) and serum sclerostin levels in chronic spinal cord injured (SCI) patients and healthy controls. SETTING: SCI centre in Italy. METHODS: Blood samples, whole-body bioelectrical impedance analysis and BMD measurement with the ultrasound technique at the calcaneus level were taken from patients suffering from chronic SCI (both motor complete and incomplete) and healthy control subjects. RESULTS: A total of 28 SCI patients and 15 healthy controls were enrolled. Serum myostatin levels were statistically higher (P<0.01) in SCI patients compared with healthy controls. Similar results were found comparing both the motor complete and the motor incomplete SCI subgroups to healthy controls. Serum sclerostin was significantly higher in patients with SCI compared with healthy controls (P<0.01). BMD, stiffness and mean T-score values in SCI patients were significantly lower than those in healthy controls. Serum myostatin concentrations in the motor complete SCI subgroups correlated only with serum sclerostin levels (r(2)=0.42; P=0.001) and ASMM (r(2)=0.70; P=0.002) but not in healthy controls. DISCUSSION: Serum myostatin and serum sclerostin are significantly higher in chronic SCI patients compared with healthy controls. They are potential biomarkers of muscle and bone modifications after SCI. This is the first study reporting an increase in serum myostatin in patients suffering from chronic SCI and a correlation with ASMM.

Heart Rate Variability (HRV) modifications in adult hemiplegic patients after botulinum toxin type A (nt-201) injection.

BACKGROUND: The most important adverse effect of BoNT-A is the systemic diffusion of the toxin. There is some evidence that the administration of high doses can increase the risk of systemic diffusion and the development of clinically evident adverse effects, however an international consensus does not exist about its maximum dose. AIM: The aim of this study was to evaluate changes in autonomic heart drive induced by high doses (higher than 600 units) of incobotulinumtoxinA injection in spastic stroke patients. Moreover, the treatment safety by monitoring adverse events occurrence was assessed. DESIGN: Case control study. POPULATION: Eleven stroke survivors with spastic hemiplegia. METHODS: Patients were treated with intramuscular focal injections of IncobotulinumtoxinA (NT 201; Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany). Doses were below 12 units/Kg. Each patient underwent an ECG recording before injection and 10 days after treatment. Linear and non-linear Heart Rate variability (HRV) measures were derived from ECGs with a dedicated software. RESULTS: None of the variable considered showed statistically significant changes after BoNT-A injection. CONCLUSION: The use of incobotulinumtoxinA in adult patients at doses up to 12 units/kg seems to be safe regarding autonomic heart drive. CLINICAL REHABILITATION IMPACT: The use of IncobotulinumtoxinA up to 600 units could be a safe therapeutic option in spastic hemiplegic stroke survivors.

The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment.

Osteoporotic fractures are a public health problem and their incidence and subsequent economic and social costs are expected to rise in the next future. Different drugs have been developed to reduce osteoporosis and the risk of osteoporotic fractures, and among them, antiresorptive agents, and in particular oral alendronate, are the most widely utilized. However, one of the most common problems with antiresorptive drugs is poor adherence to treatment, which is associated with a high fracture incidence and with an increase in hospitalization costs. One of the main reasons of poor adherence to these treatments is the occurrence of adverse events, mainly at gastrointestinal (GI) level, including dyspepsia, dysphagia, and esophageal ulcers. In light of these considerations the aim of this paper is to perform a literature review to show the pathophysiologic bases of GI alendronate-induced adverse events and how new bisphosphonate formulations like effervescent alendronate can improve compliance and persistence to treatment and decrease the fracture rate incidence in osteoporotic patients.

OnabotulinumtoxinA and multiple sclerosis.

Lower urinary tract dysfunction is present in two of three patients with multiple sclerosis five years after the diagnosis. Most frequent symptoms are related to neurogenic detrusor overactivity, often associated with detrusor-sphincter dyssynergia. From the end of the 1990s, there is growing evidence that neurogenic detrusor overactivity can be effectively managed by intradetrusorial injections of botulinum toxin type A. This treatment has shown, in different randomised placebo-controlled trials, to be safe and effective on clinical and urodynamic parameters with significant improvement in quality of life. The median duration of effect is in mean nine months. The vast majority of studies have been conducted with onabotulinumtoxinA. The dose of onabotulinumtoxinA commonly used to treat neurogenic detrusor overactivity in patients with multiple sclerosis is 200 UI, even if in selected patients lower doses can be preferred. To be considered eligible for treatment, all patients should accept and be instructed to perform clean intermittent self-catheterisation, since the risk of increased post-void residual volume and/or urinary retention after injection is high, especially with 200 UI of onabotulinumtoxinA. However, quality of life and patient satisfaction seem not to be affected by the need of intermittent catheterisation. The risk of urinary infection after the procedure is to be kept in mind, mainly in patients with multiple sclerosis, so that adequate antibiotic prophylaxis is highly recommended.

Possible synergism of physical exercise and ghrelin-agonists in patients with cachexia associated with chronic heart failure.

The occurrence of cachexia of multifactorial etiology in chronic heart failure (CHF) is a common and underestimated condition that usually leads to poor outcome and low survival rates, with high direct and indirect costs for the Health Care System. Recently, a consensus definition on cachexia has been reached, leading to a growing interest by the scientific community in this condition, which characterizes the last phase of many chronic diseases (i.e., cancer, acquired immunodeficiency syndrome). The etiology of cachexia is multifactorial and the underlying pathophysiological mechanisms are essentially the following: anorexia and malnourishment; immune overactivity and systemic inflammation; and endocrine disorders (anabolic/catabolic imbalance and resistance to growth hormone). In this paper, we review the main pathophysiological mechanisms underlying CHF cachexia, focusing also on the broad spectrum of actions of ghrelin and ghrelin agonists, and their possible use in combination with physical exercise to contrast CHF cachexia.

Sarcopenia or muscle modifications in neurologic diseases: a lexical or patophysiological difference?

Sarcopenia is a condition characterized by a decrease in muscle mass and function (strength and mobility) that is frequently observed in the elderly. In people with paresis and altered mobility due to central nervous system (CNS) diseases, this definition then may not be applicable. In CNS diseases, mainly stroke and spinal cord injury, different and specific patterns of muscle loss and muscle changes have been described, due to denervation, disuse atrophy, spasticity and myosteatosis. The main observations available about these phenomena in CNS diseases are reviewed, and a broad view on the specific physiopathological mechanisms is also described. Moreover, a description of the potential pharmacological targets and treatment strategies (physical and nutritional) is provided. Since sarcopenia of the elderly and muscle modifications and muscle atrophy in CNS diseases have different mechanisms, it is probable that they do not respond equally to the same treatments.

The value of adding mirror therapy for upper limb motor recovery of subacute stroke patients: a randomized controlled trial.

BACKGROUND: Upper limb paresis remains a relevant challenge in stroke rehabilitation. AIM: To evaluate if adding mirror therapy (MT) to conventional therapy (CT) can improve motor recovery of the upper limb in subacute stroke patients. DESIGN: Prospective, single-center, single-blind, randomised, controlled trial. SETTING: Subacute stroke patients referred to a Physical and Rehabilitation Medicine Unit between October 2009 and August 2011. POPULATION: Twenty-six subacute stroke patients (time from stroke <4 weeks) with upper limb paresis (Motricity Index ≤ 77). METHODS: Patients were randomly allocated to the MT (N.=13) or to the CT group (N.=13). Both followed a comprehensive rehabilitative treatment. In addition, MT Group had 30 minutes of MT while the CT group had 30 minutes of sham therapy. Action Research Arm Test (ARAT) was the primary outcome measures. Motricity Index (MI) and the Functional Independence Measure (FIM) were the secondary outcome measures. RESULTS: After one month of treatment patients of both groups showed statistically significant improvements in all the variables measured (P<0.05). Moreover patients of the MT group had greater improvements in the ARAT, MI and FIM values compared to CT group (P<0.01, Glass's Δ Effect Size: 1.18). No relevant adverse event was recorded during the study. CONCLUSION: MT is a promising and easy method to improve motor recovery of the upper limb in subacute stroke patients. CLINICAL REHABILITATION IMPACT: While MT use has been advocated for acute patients with no or negligible motor function, it can be usefully extended to patients who show partial motor recovery. The easiness of implementation, the low cost and the acceptability makes this therapy an useful tool in stroke rehabilitation.

A prospective observational study of the clinical efficacy and safety of intra-articular sodium hyaluronate in synovial joints with osteoarthritis.

BACKGROUND: Clinical trials have demonstrated the safety and efficacy of hyaluronic acid-based products for the treatment of synovial joints affected by osteoarthritis (OA), but data from observational studies of normal medical practice are sparse. AIM: This study investigated the safety and efficacy of intra-articular (IA) sodium hyaluronate (MW 1500-2000 KDa; Hyalubrix®) in the treatment of synovial joint OA. DESIGN: This is prospective, and observational study. SETTING: This study was carried out at 47 specialist centers for physiatrists, orthopedics and rheumatology in Italy; the enrolled population, 1266 outpatient, was predominantly female (66%, 840/1266), with a mean age of 66 years, and a mean weight of 74 kg. POPULATION: The Participants with OA received IA injections of the study treatment (2 mL) once per week for 3 weeks. The knee was the joint most commonly affected by OA (right knee 802/1266 [63%]; left knee 598/1266 [47%]), and the longest median duration of disease occurred in the carpal joint (right carpal joint 40 months; left carpal joint 60 months). METHODS: The primary endpoints were tolerability and details of usage of the IA sodium hyaluronate syringe device. Efficacy parameters included assessment of self-reported pain via the Visual Analogue Scale (VAS), and evaluation of motor function via the Health Assessment Questionnaire (HAQ). Quality of life (QoL) was assessed using the Euro QoL questionnaire (Clinical Trial Registration Number: ISRCTN 42690497). RESULTS: Data from 1266 participants were collected. The adverse event (AE) rate was 0.8% (95% CI, 0.4 to 1.5). Thirteen AEs were reported, 12 of which were mild or moderate in severity. Only one participant discontinued study treatment following an AE. No serious adverse events occurred. Coadministration of local anesthetic was required by up to 10% of patients. Statistically significant improvements in VAS, HAQ and EuroQoL were recorded in multiple joints (P<0.0001 for each). CONCLUSION: The study treatment was safe and well tolerated. CLINICAL REHABILITATION IMPACT: . The study treatment reduced pain, improved mobility, and increased QoL in participants with OA.

Extensor hallucis longus transfer as an alternative to split transfer of the tibialis anterior tendon to correct equinovarus foot in hemiplegic patients without overactivity of tibialis anterior.

This study assessed if transfer of the extensor hallucis longus is a valid alternative treatment to split transfer of the tibialis anterior tendon in adult hemiplegic patients without overactivity of the tibialis anterior. One group of 15 patients had overactivity of tibialis anterior in the swing phase, and underwent the split transfer. A further group of 14 patients had no overactivity of tibialis anterior, and underwent transfer of extensor hallucis longus. All patients had lengthening of the tendo Achillis and tenotomies of the toe flexors. All were evaluated clinically and by three-dimensional gait analysis pre- and at one year after surgery. At this time both groups showed significant reduction of disability in walking. Gait speed, stride length and paretic propulsion had improved significantly in both groups. Dorsiflexion in the swing phase, the step length of the healthy limb and the step width improved in both groups, but only reached statistical significance in the patients with transfer of the extensor hallucis longus. There were no differences between the groups at one year after operation. When combined with lengthening of the tendo Achillis, transfer of the extensor hallucis longus can be a valid alternative to split transfer of the tibialis anterior tendon to correct equinovarus foot deformity in patients without overactivity of tibialis anterior.

Intrathecal baclofen bolus complicated by deep vein thrombosis and pulmonary embolism. A case report.

The aim of this study was to present a case of deep vein thrombosis (DVT) and pulmonary embolism (PE) after an intrathecal baclofen bolus test. The study was carried out at a tertiary care rehabilitation center in Italy, and it reports a case of a 65-year-old woman affected by primary lateral sclerosis, with lower limb spasticity, who underwent an intrathecal baclofen bolus trial. After a 100 microg baclofen test, she developed hypotension and oxygen desaturation lasting two days. A Doppler ultrasonography was positive for DVT, and echocardiography confirmed the diagnosis of PE. A Doppler ultrasonography performed before the test was negative. This is the first report in the literature of DVT and PE after an intrathecal baclofen bolus trial. Clinicians and patients should be informed that the intrathecal baclofen bolus trial procedure could be associated with rare but important risks such as DVT and PE, and they should be alert in recognizing potentially life-threatening complications.

Selective neuromuscular blocks and chemoneurolysis in the localized treatment of spasticity.

Selective neuromuscular blocks and chemoneurolysis are currently the most widespread therapies for treating localized or locoregional spasticity. Both procedures present advantages and disadvantages. The main advantages of BTX-A are its relative ease of use, low incidence of side effects, reversibility and elevated efficacy. Its disadvantages are the limited maximum dose, which does not permit the treatment of many muscles simultaneously, especially if they are large, and its relatively high cost. Phenol neurolysis has a low cost, elevated efficacy in the control of pathologic muscle overactivity, and long duration of effect. Its disadvantages are the risk of injury to the vascular and sensory structures and the difficulty in performing the procedure. The risks associated with neurolysis have led to an increasing interest in and use of BTX-A, making it one of the most widely used therapies in treating localized spasticity. From the perspective of a balanced benefit-risk analysis, a viable option for some cases may be to combine phenol neurolysis for treating spasticity in large proximal muscles and BTX-A for treating hypertonia in small distal muscles.

The menopausal age, related factors and climacteric symptoms in Turkish women.

An interview based survey to reveal age at menopause and associated factors was conducted in a clinic based sample of Turkish women living mainly in an urban area. Interviews by a psychologist were obtained from 1500 women aged 41-70. The study included only women who had undergone natural menopause and had their last menstrual bleeding at least 1 year previously. The mean and median age at menopause was 47.8 +/- 4.0 and 51, respectively. Parity and BMI had a statistically significant impact on the age of menopause (P = 0.0397 and 0.0403). The most common symptoms were muscle and- or joint and- or bone pain (82.3%) and hot flushes (73.9%). Although the population was clinic based, this study is the first one of its kind in Turkish women.