Efficacy of botulinum toxin A in upper limb function of hemiplegic patients

Botulinum toxin A has been reported to reduce spasticity and increase the comfort of hemiplegic patients. The aim of this study was to assess the efficacy of the treatment on disability, especially in manual activities, and to attempt to identify predictive factors of improvement. Twenty patients (mean age: 54.4 years; M: 14; right hemiplegia: 12) were included, with a delay of at least three months after unilateral hemispheric stroke. Botulinum toxin A (BOTOX) was injected into the arm adductors (8 cases), forearm flexors (17 cases), pronators, wrist and finger flexors (20 cases),with a total dose of 200 to 300 U. Examination (day 1 and 15, month 2 and 5) consisted of spasticity assessment (modified Ashworth scale), muscle strength, passive range of motion (goniometry), and pain, followed by functional tests, especially the Rivermead Motor Assessment (RMA) and Nine-hole Peg Test (NHPT). Performance in daily living was assessed with the Functional Independence Measure (FIM), and an original analysis of hand grasp, grip and pinches used in domestic activities (9 items), and of comfort of patients and caregivers. Significant reduction in spasticity was observed on the elbow flexors, pronators, wrist and fingers flexors, especially at day 15 (mean 0.90 to 1 point), with wide variations in effect. Muscle strength was increased in wrist and fingers extensors, with concomitant increase in the opening of the thumb to index finger space. There was no effect on the NHPT requiring distal manipulation, but the RMA, which especially concerned picking up and releasing a tennis ball, showed significant improvement. Furthermore, use of the upper limb in daily living increased, particularly for internal grasping of objects, and for grasping by the top, transporting and releasing of objects. Patients and caregivers re ported facilitation in dressing, and in proximal and distal care of the upper limb. The global flexor position of the limb improved. Ad verse reactions were rare and mostly consisted of transitory pain during injection. The improvement in the RMA was better explained by the quality of the initial motor command on distal prehension (positive correlation with motor strength), and that in hand using in domestic activities by a lower level of spasticity on pronators and wrist flexors (negative correlations with spasticity). Conversely, the severity of the motor deficit (negative correlations with motor strength) and a high level of spasticity before injection (positive correlations with spasticity) mostly explained the improvement in comfort. In conclusion, botulinum toxin A is efficient in improving hand use in patients with relatively preserved distal motricity, and in increasing comfort in patients with severe global disorders.     

Levodopa and bromocriptine in hypoxic brain injury

Background: Postanoxic encephalopathy is frequent in patients presenting with abrupt cardiac arrest or respiratory failure. Little is known about the effectiveness of oral medications on the cognitive and motor consequences. Objective: To present data suggesting partial improvement after administration of levodopa/benserazide. Methods: After observing partial benefit in one case, each patient admitted to rehabilitation following brain anoxia was systematically treated with levodopa/benserazide (200/50 to 400/100 mg/day), then bromocriptine (15 mg/day). Results: In the first patient, brain anoxia was severe, with secondary agitation, quadriparesis, involuntary movements, inattention and communication disorders. Introduction of levodopa/benserazide resulted in reduction of agitation and involuntary movements and improvement of communication, thus facilitating care and rehabilitation efforts. A weaning test resulted in rapid worsening. The four following patients also presented with anoxia of variable severity. Marked improvement was observed in case 2, presenting with agitation, loss of orientation, amnesia, postural disorders, involuntary movements and dysphagia, with a withdrawal test resulting in immediate re-enhancement of symptoms. Modest improvement was observed in patient 3, who had hypokinesia, rigidity, adynamia, impaired attention, and reduced verbal fluency. Patient 4 presented with memory disorders without motor difficulties: mild improvement was observed in daily life and memory tests. In patient 5 who also presented with severe memory disorders, the benefit was absent. In each case, bromocriptine was introduced 3–4 weeks following levodopa, but without additive effect. Both treatments could be interrupted after a few months, without worsening. Conclusions: Levodopa and benserazide can be of benefit in the few months following brain anoxia, especially on some of the motor disorders and apathy, but the benefit is inconstant and modest on memory disorders. Anoxia could alter dopaminergic mesencephalic systems, which activate the striatal and mediobasal frontal cortex, and these disorders could be partially reversible by medical treatment. Received: 31 January 2002, Received in revised form: 6 June 2002, Accepted: 12 June 2002 Correspondence to Dr. Marc Rousseaux     

Neurofeedback treatment of epilepsy

With electroencephalographic (EEG) biofeedback (or neurofeedback), it is possible to train the brain to de-emphasize rhythms that lead to generation and propagation of seizure and emphasize rhythms that make seizures less likely to occur. With recent improvements in quantitative EEG measurement and improved neurofeedback protocols, it has become possible in clinical practice to eliminate seizures or reduce the amount of medication required to control them. In this article, the history of neurofeedback for epilepsy is presented followed by discussions of the relevant neurophysiology of epilepsy. A model of how neurofeedback might raise the seizure threshold is then presented. Clinical experience using a quantitative EEG-guided approach is described, including a representative case study.     

Clinical results from transplanting incompatible live kidney donor/recipient pairs using kidney paired donation

Context  First proposed 2 decades ago, live kidney paired donation (KPD) was considered a promising new approach to addressing the shortage of organs for transplantation. Ethical, administrative, and logistical barriers initially proved formidable and prevented the implementation of KPD programs in the United States. Objective  To determine the feasibility and effectiveness of KPD for the management of patients with incompatible donors. Design, Setting, and Patients  Prospective series of paired donations matched and transplanted from a pool of blood type or crossmatch incompatible donors and recipients with end-stage renal disease (6 conventional and 4 unconventional KPD transplants) at a US tertiary referral center (between June 2001 and November 2004) with expertise in performing transplants in patients with high immunologic risk. Intervention  Kidney paired donation and live donor renal transplantation. Main Outcome Measures  Patient survival, graft survival, serum creatinine levels, rejection episodes. Results  A total of 22 patients received transplants through 10 paired donations including 2 triple exchanges at Johns Hopkins Hospital. At a median follow-up of 13 months (range, 1-42 months), the patient survival rate was 100% and the graft survival rate was 95.5%. Twenty-one of the 22 patients have functioning grafts with a median 6-month serum creatinine level of 1.2 mg/dL (range, 0.8-1.8 mg/dL) (106.1 µmol/L [range, 70.7-159.1 µmol/L]). There were no instances of antibody-mediated rejection despite the inclusion of 5 patients who were highly sensitized to HLA antigens due to previous exposure to foreign tissue. Four patients developed acute cellular rejection (18%). Conclusions  This series of patients who received transplants from a single-center KPD pool provides evidence that recipients with incompatible live donors, even those with rare blood type combinations or high degrees of HLA antigen sensitization, can receive transplants through KPD with graft survival rates that appear to be equivalent to directed, compatible live donor transplants. If these results can be generalized, broader availability of KPD to the estimated 6000 patients with incompatible donors could result in a large expansion of the donor pool.      

Variability and predictability of functional efficacy of botulinum toxin injection in leg spastic muscles

Botulinum toxin injection reduces spasticity level. However, the effects on gait parameters and daily living activities remain controversial, and the prediction of results remains poorly evaluated. The aim of this open study was to investigate these effects, and the predictability of results. Forty-seven injections were given to 47 patients with stroke (males: 24; mean age: 51.7), in the soleus, gastrocnemius, tibialis posterior and anterior, and flexor digitorum longus, with a global dose of 300 U (Botox). Each was evaluated at day 1 (D1), day 15 (D15), month 2 (M2) and month 5 (M5). We observed a significant but moderate reduction in spasticity (Ashworth) of the ankle plantar flexors (0.72/5) and dorsiflexors, which was greater at D15, and an improvement in distal positioning in the upright situation. Upright balance and gait (Functional Ambulation Categories) were improved, especially at M2 and in the barefoot condition. Gait velocity and step length with usual aids (10 m) were discretely increased, and this was especially evident in about 15 patients. We also found improvement in the Rivermead Motor Assessment. Patients reported better foot positioning, facilitation in limb propulsion, and better static and dynamic balance. For each assessment, high variability in the effects was also shown. Improvement in functional tests was partially predicted by age (negative relation), delay since stroke (negative relation), gender (better in men), spasticity of hip adductors and knee extensors (negative relation), active ankle dorsiflexion (positive relation) and heel-ground distance (positive relation). In conclusion, the effects on spasticity, balance and gait were relatively modest, and with a large variability between patients. Functional improvement could be partially predicted by several general or specific factors, the knowledge of which is important in the selection of patients to be injected, and for future trials aiming to demonstrate the efficacy of botulinum toxin injection.     

The effect of filter vent blocking and smoking topography on carbon monoxide levels in smokers

Two studies were conducted to examine the effect of filter vent blocking and smoking topography on carbon monoxide (CO) levels in smokers. In Study 1, 12 participants smoked two types of cigarettes (Marlboro Light and Carlton 100) under two types of blocking conditions (unblocked and half-blocked) while using a smoking topography device. Participants were restricted to 8 puffs, separated by 45 s. Significant main effects of CO boost for cigarette type and blocking condition replicated previous findings. A significant increase in CO boost for the Marlboro Light blocked condition is a novel finding for this best-selling brand. That result and the finding that topography measures did not predict CO boost made us question the reliability of CO boost. In Study 2, we examined the reliability of CO boost by recruiting 12 participants to smoke three unblocked Carlton 100 cigarettes in one session and three half-blocked in another. CO boost was significantly greater for the blocked sessions compared to the unblocked and CO boost did not differ within session, thus supporting the reliability of the measure. When participants do not switch brands within a session, smoking topography measures are predictive of CO boost.     

Childhood obesity and insulin resistance in a Yucatan mini-piglet model: putative roles of IGF-1 and muscle PPARs in adipose tissue activity and development

OBJECTIVE: To explore metabolic and cellular modifications induced during childhood obesity, in a novel animal model of obese mini-piglets. DESIGN: A total of 10 four-month old Yucatan mini-pigs were followed from prepuberty to adulthood. Animals were divided into two groups. The first one had been overfed (OF) a western-type diet and the second one had been normally fed a control recommended human-type diet (NF). MEASUREMENTS: Plasma insulin-like growth factor 1 (IGF-1), insulin, leptin, nonesterified fatty acids, triglycerides (TGs) and glucose were determined at sexual maturity and at young adulthood. Quantitative gene expressions of peroxysome-proliferator-activated receptors (PPARs), glucose transporter 4, insulin receptor, IGF-1, leptin and interleukin-6 (IL-6) in skeletal muscle, adipose tissue and liver were also measured at both stages. Adult insulin sensitivity was measured via euglycaemic-hyperinsulinaemic clamps. RESULTS: Increased body weight in adult OF pigs was associated with increased body size and low insulin sensitivity. Sexually mature OF pigs had higher IGF-1 plasma concentrations than their lean littermates (P < 0.05). In the OF group, TGs and glucose were both decreased (P < 0.05). Muscle PPARgamma and alpha in OF pubescent pigs as compared to NF pigs were 11 times higher and 20 times lower, respectively (P < 0.01). CONCLUSION: Obesity and insulin resistance induced by overfeeding mini-pigs during development and puberty were not associated with the cluster of metabolic modifications frequently observed in their adult littermates. Increased IGF-1 concentrations and modifications of skeletal muscle PPAR (alpha and gamma) expressions may help the young obese pig to partially regulate its glycaemia and triglyceridaemia through an increase of fat mass, which maintains its high insulin sensitivity.